Great. Welcome, everyone. My name's Jessica Fye. I'm a biotech analyst here at J.P. Morgan, and we are continuing the 43rd annual healthcare conference today with Legend. You're going to hear a presentation from the company, and then we're going to go into some Q&A.
If you have a question in the room, just raise your hand. Someone will bring you a microphone, or you can send them to me on the iPad up here via the portal. So with that, let me turn it over to Legend's CEO, Ying Huang.
Thank you, Jess, and thanks to JPMorgan for inviting Legend Biotech. So this is our standard safe harbor disclaimer. For those who are not familiar with Legend, I'll just give a very quick overview of the company. So today, Legend is the largest standalone cell therapy company with over 2,500 employees across three continents, and we're a pioneer in treatments that change cancer care.
We are at the forefront of the CAR-T therapy revolution with our legendary treatment called Carvykti, which is a one-time injection for the treatment of multiple myeloma a nd we develop, manufacture, and also co-commercialize with our partner, Johnson & Johnson in the U.S. Carvykti to date has been the fastest launch among all FDA-approved CAR-T therapies. T hen lastly, we have built an end-to-end cell therapy company based in the U.S., and we're expanding our leadership to maximize the Carvykti potential.
A few things to highlight: how we are a proven leader in the cell therapy space on a path to cure. To date, we have treated more than 4,500 patients with Carvykti, and Carvykti is the first and only CAR-T therapy providing superior survival benefit over a standard of care in a randomized Phase III trial in a second-line multiple myeloma setting.
Carvykti continues to be the most successful CAR-T launch to date, generating about $286 million in global sales in the third quarter of 2024, which was the 10th quarter since FDA approval in February of 2022 a nd recently, we and J&J have been focusing our efforts on the second-line launch and penetration into early lines of therapy in this setting, educating community hematologists and oncologists about the benefit of Carvykti. A lso, we're trying to increase the use of outpatient setting.
We've made a lot of progress on all these fronts I just mentioned, and we have just scratched the surface. We're addressing a significant unmet medical need in the treatment of multiple myeloma. The incidence in the U.S. alone is about 36,000 cases of new diagnoses every year, and the median survival for patients who have failed three major classes of therapy in the market today before BCMA targeting modality was introduced into market was shorter than 12 months.
As many of you already know, we entered into a global collaboration agreement with Johnson & Johnson in December 2017 to address this unmet medical need in multiple myeloma. We have a cost-sharing and profit-split arrangement with J&J, which you can see in this slide. J&J has been a great partner for Legend.
Within multiple myeloma, J&J is the number one player in the global market, and Carvykti is shaping to become a foundation therapy in that portfolio. This has translated into deep experience in both the community and academic settings. Here in this slide, it's a snapshot of the unique profile of Carvykti, which is the first and only CAR-T therapy in multiple myeloma to achieve a significant and also clinically meaningful survival benefit over standard of care in a Phase III setting.
We're working to have this important update, including the label, in 2025 in both the U.S. and in Europe. Turning next, I want to focus on our plans to maximize multiple myeloma market leadership for Carvykti. You can see this is our record launch trajectory among CAR-T therapies. This slide actually includes the launch performance for all six FDA-approved CAR-T therapies.
With our fifth-line launch back in 2022, we became the market leader, and our successful launch is a model for the ongoing second-line launch and beyond. The next slide illustrates the global uptake for Carvykti. We continue to drive demand for and also supply of Carvykti since our approval in second-line last year and also the expansion of manufacturing capacity.
We have accelerated the growth both in the U.S. and globally with 88% year-over-year growth in the last quarter we reported, which is the third quarter of 2024. We have also recently welcomed a new leader for our manufacturing and commercial areas, Alan Bash, who will singly focus on maximizing the potential of Carvykti in 2025 and beyond.
The U.S. market remains a primary area of focus for us, but we have been gradually expanding our presence in Europe as well as with the initiation of clinical and commercial production recently at our first facility in Ghent, Belgium. We're proud to have the most extensive lifecycle management and also development program in cell therapy with more than 2,000 patients enrolled in the CARTITUDE-2 clinical program.
To that end, we have several early line studies, including CARTITUDE-2, which is a Phase II multicohort trial, and CARTITUDE-5 and also CARTITUDE-6 study in the front line. These studies are well on the way, designed to generate new indications for Carvykti. We're looking forward to sharing data in the newly diagnosed setting when the studies are complete.
Notably, our CARTITUDE-5 trial, which is testing Carvykti versus standard of care in the setting of transplant-ineligible or transplant-deferred patients, we have already completed global enrollment last year. With our second-line approval recently, we have the opportunity to treat more than 100,000 patients, and we do see a tremendous opportunity to make a difference for more patients than ever, given we have only treated a small fraction of those patients to date.
Carvykti can be administered in both inpatient and also outpatient settings because of its unique late onset of CRS. Physicians are able to utilize outpatient administration for Carvykti to support patient needs and also hospital infrastructure. Today, Carvykti is available in 97 authorized treatment centers in the United States. Outpatient setting represents approximately 48% of our volume in the third quarter compared to 30% almost a year ago. On this side, you will see our supply map.
We have discussed our four-node approach to the manufacturing, but as a reminder, CAR-T manufacturing is complex. We're pioneering an undertaking that has never been done in the treatment of multiple myeloma. If you look at this global supply map, in the U.S., our main commercial facility is located in Raritan, New Jersey. That's where we have been manufacturing clinical supplies since 2019.
Our CMO, Novartis, began clinical production in the summer of 2024 in New Jersey, and we expect commercial production to begin in the first half of this year pending FDA approval. On the right side of the slide, we have initiated both clinical and commercial production at our first site called Obelisc in Ghent, Belgium, which is at the bottom, and we plan to begin production this year in another much larger greenfield facility called Tech Lane in the same city, Ghent, Belgium.
Moving to this slide, you can see our upcoming milestones in expanding our manufacturing capacity. We continue to work towards doubling our commercial supply again this year versus what our supply was in 2024. We also expect FDA approval on the physical expansion of our facility in Raritan, New Jersey, by the end of this year.
We're thrilled that we're having the most successful CAR-T launch to date, but we're working hard to bring Carvykti to all the potential patients who might benefit from its unprecedented efficacy and ease of administration. The studies we have underway and our manufacturing expansion will enable us to maximize the benefit of Carvykti.
Beyond Carvykti, we're also leveraging our research and development capabilities in building next-generation CAR-T therapies. We look to use the successful model we have developed, Carvykti, and take it to other therapeutic areas where options are limited.
We're leveraging our end-to-end R&D capability across three key areas. The first is on blood cancers and also next-generation multiple myeloma therapies, including allogeneic and in vivo CAR-T therapies. The second is on solid tumor indications, such as through our partnership with Novartis on the DLL3 program, which we'll discuss shortly.
F inally, we have also initiated phase I study for our first autoimmune indication where CAR-Ts have not been approved yet. We do see significant commercial opportunities. I would like to also further highlight our end-to-end R&D capabilities I just talked about. First, we have a unique armoring strategy.
For example, in our DLL3 program that's partnered with Novartis, we use a tandem binder design and an armor to improve the penetration of the CAR-T cells into the organ, in this case, the lungs, to overcome the immunosuppressive tumor microenvironment.
Second, we have an excellent in-house antibody screening and engineering capability that's exemplified by the structure of Carvykti. It took us two years and hundreds of constructs to screen before we started our first in-human study back in 2016. F inally, we have a diverse platform for allogeneic therapies, including alpha beta T cells, gamma delta T cells, and NK cells.
As most of you know, we announced a partnership in November 2023 with Novartis to advance certain DLL3-targeted CAR-T therapies. We received a $100 million upfront payment and are eligible to receive up to $1 billion in future milestone payments. Once the product is commercialized, we're eligible to receive tiered royalty payments from Novartis. Through this partnership, we're able to combine our best-in-class binder design and our knowledge of DLL3 biology with the T-Charge fast manufacturing technology developed by Novartis.
Why is that important? The T-Charge manufacturing technology is particularly important in this indication for small cell lung cancer, which accounts for approximately 15% of all lung cancer diagnoses in this country. The standard front-line therapy is chemotherapy with a median progression-free survival in the neighborhood of 10 months.
After the patient relapses from chemotherapy, it becomes a rapidly progressive disease, and that is why it's so important to use this fast manufacturing technology developed by Novartis for this indication. As it relates to the ongoing Phase I study for LB2102 we're running, we're actually actively treating and enrolling patients at four different clinical sites in the U.S. After Phase I, Novartis will take over, and they will conduct any further development, including manufacturing and future commercial activities.
Turning to our next program in IND in the U.S., LB1908, which is an auto CAR-T targeting a protein called Claudin 18.2, and that's overexpressed in gastric, pancreatic, and esophageal cancers. For the Phase I study, we are in active enrollment and treating patients at six different clinical sites in the U.S.. We have a number of important milestones coming up both for Carvykti and beyond.
First of all, we are working to include the overall survival benefit in the label, which is the gold standard for all doctors. We're continuing to increase our manufacturing capacity in New Jersey and in Belgium, as well as our CMO at Novartis, to meet the increasing demand for Carvykti. F inally, we look forward to sharing data from CARTITUDE-5 studies, and we'll continue to enroll CARTITUDE-6 studies and advance our early-stage programs.
In conclusion, Carvykti is the proven leader among CAR-T therapies in multiple myeloma, forging the path of cure. We're committed to building upon the most successful CAR-T launch to date, and we look forward to executing our strategy to maximize the commercial opportunity for Carvykti and to providing you with updated data this year. With that, I just want to thank you for your attention, and Jessica, I'm sure you have questions for me.
Great. So last year marked the approval in second-line for Carvykti. What is the next milestone for this franchise that's going to rival an event like that?
I think, first of all, like I mentioned in the prepared remarks, we're just scratching the surface for second-line because if you look at the three major markets for CAR-T therapies, namely the U.S., Western Europe, and Japan, you're looking at about 100,000 patients per year. That's the patient floor or the addressable market for us.
Yet we have treated, like I said, so far 4,500 patients to date in the last few years. So we believe that we'll continue to deepen our penetration into the community and also into the second-line setting, a nd to that end, we're very happy that right now, if you look at the revenue mix, approximately half of our incoming orders are from the CAR-T4 indication, which is second to fourth line.
W e believe that by the end of this year, the majority of the patients who are treated with Carvykti in the U.S. will come from that early line indication. So that is a very important goal for the company and also for our partner at J&J.
Great. I feel like we've spent a lot of time over the past couple of years talking about manufacturing capacity. Can you take us through where Legend ended 2024 with from a capacity standpoint? What's the volume goal you expect to achieve by the end of 2025, and where could it go from there?
Sure. We continue to be in the so-called supply constraint situation. I can tell you that last year, overall, our utilization rate for the Raritan facility was 96%, a nd since May of last year, following the second-line approval by the FDA, our plant has been running at 100% utilization. We don't even lose one single slot that's approved by the FDA in the last year.
W e continue to see the situation here because there's a queue we're actually seeing in almost every step of the way because we're facing unprecedented demand from the early line and also the fifth-line old indication. So our goal, in fact, that's what I think J&J and Legend talked about two years ago at this conference, remains to be the same, which is we'll achieve 10,000 doses per year capacity by the end of this year.
I can tell you at this point, we're solidly on track to deliver that. Maybe I'll give you a little bit of detail about how we get there. First of all, we're actually implementing the ongoing ramp-up recently that's approved by the FDA for the Raritan site. Secondly, we've broken ground pretty much for the physical construction for expansion for Raritan, where we're planning to double the manufacturing square footage for the suites.
We're expecting the FDA to approve our expansion to start commercial production by the end of this year. That's what's happening in the Raritan site, which, by the way, is the world's largest cell therapy manufacturing site. Secondly, Novartis started the clinical trial production in the summer of last year after the FDA approval. Right now, we're awaiting FDA approval again for commercial license for Novartis to start commercial production for Carvykti.
That should happen in the first half of this year. Once that happens, we're expecting a pretty meaningful boost in our capacity. T hirdly, for the Tech Lane Greenfield facility in Belgium, we're expecting clinical production to start in this quarter pending EMA approval. T hen following that, we expect the commercial approval to be approved by the regulatory authorities by the end of this year. That's how we go from where we are today to 10,000.
Great. You touched on this a little bit, but I wonder if we can spend a little more time here as you kind of shift the patients being treated with Carvykti from the super, super late line to earlier lines. What proportion of patients by the end of 2025 do you think will be in that kind of second-line plus CAR-T4 setting?
Yeah. So we received FDA approval in April of last year. In the last two quarters, as we commented on the third quarter financial earnings call, we already saw nearly half of our incoming orders based on the fourth-line indication. That is actually a very pleasant surprise because we actually did not expect the uptake for second-line to fourth-line so quickly from the community and also from the tertiary centers.
So this year, we set a very aggressive goal that we believe at least two-thirds or maybe even three-quarters of our incoming order by the end of this year should come from early line, second to fourth line, because our competition strategy is always that we want to leapfrog our competition and also potential competition by getting into the second line as early as possible.
So that is our goal. I think at this point, based on the feedback from the field, we're pretty much on track to deliver that by the end of this year.
Okay. You mentioned competition. Can you walk through why you think Carvykti should remain the market leader in BCMA CAR-T?
Yeah, absolutely. I think we have a compelling argument here. Number one, Carvykti today is the only and first CAR-T that realized this significant benefit in improving survival versus standard of care in a randomized global Phase III study. L ike I said in the prepared remarks, we at J&J are working hard to include that label in the U.S. and also in the FDA and EMA label by the end of this year.
So we will go out and be able to talk about the benefit of improving survival in this case. That is the number one benefit. I think, again, we're not matched by any other therapies in the field today. S econdly, we're working hard to continue to increase our manufacturing capacity here.
Like I said, by the end of this year, we feel really confident that we'll be able to deliver a total capacity in our four nodes at 10,000 doses per year. La stly, which shouldn't be taken lightly, we have seen consistent benefit and also managed safety in more than 4,500 patients. We feel really good about the strength of our data and also the consistency in the performance of Carvykti.
I guess while we're talking about kind of competitive positioning, when do you think your competitor could see their first case of Parkinsonism if they haven't already?
I'm not in the business of projecting what competition could achieve, but I do want to, again, since we're talking about the strength of our data, right? This table here summarizes the key Phase III data that was enabling FDA approval for all major drugs in the treatment of multiple myeloma, including Carvykti in CARTITUDE-4, Abecma in KarMMa-3, and also those clinical trials in Phase III setting that enabled the approval from FDA for Pomalyst, Darzalex, Velcade, Kyprolis.
So these are all major Phase III trials, a nd you can see, hands down, we have the best hazard ratio because in PFS, compared to a three-drug cocktail such as DPD, which is a DPD, which is a three-drug cocktail of Darzalex, the number one selling drug in myeloma, by the way, Pomalyst and Dexamethasone, we were able to reduce the risk of progression of death by 71%.
Then if you look at the right side of this, we're also able to show in the first analysis for survival, we hit the statistical significance and also a clinically meaningful result. We're able to show that compared to DPD, we can reduce the risk of death by 45%. A gain, we have listed all the hazard ratios.
You guys can parse out why we say Carvykti has the best in class. This is backed by data, not any hypothesis from any claim from potential competition. We feel really good because I think even a patient who understands sixth-grade math would understand why he or she should choose Carvykti based on these numbers.
It sounds like part of the way this is going to become a really big drug is treating patients in the outpatient setting. Can you walk through what Legend and Johnson & Johnson are doing to help encourage more patients to be treated outpatient?
Yeah. As you know, like I said, we only launched the drug back in the first quarter of 2022. We only received the second-line label in April of last year. Within two quarters of the second-line approval, we're seeing about up to 48% of our use in the outpatient setting a nd J&J will report that quarter next week.
I n our next earnings call, we'll talk about where we're actually seeing increasing use of our patient use for Carvykti because of the unique late-onset CRS. So among all these six or seven FDA-approved CAR-T brands, we're the only one that can claim this wide, extensive use in the outpatient setting, which provides convenience for patients, which also achieves significant savings for the system.
I noticed in the competitor iMMagine-1 data, it seems like some patients were also treated outpatient in that trial. I guess, will Carvykti's delayed-onset CRS enabling outpatient treatment remain a competitive edge?
Yeah, absolutely, b ecause if you look at that data set, it's in fewer than 100 patients with a relatively short follow-up. They have six or eight patients who have been treated in the outpatient setting. Like I mentioned, we have treated more than 4,500 patients, and we have nearly half of the use already today in the real-world setting, in the commercial setting that is administered in the outpatient setting.
So in terms of what we're doing to support that use, A, we are educating centers and also community-based physicians the protocol, how to use Carvykti in the outpatient setting. S econdly, because of the wealth of experience we have in both clinical trials in CAR-T program and also in the real-world setting, we're able to show them, "Hey, you really can do this."
In fact, there are centers such as Johns Hopkins University Hospital or Sarah Cannon Hospital. They use only Carvykti in the BCMA CAR-T setting, and they only use it in 100% outpatient setting. That proves to you that clearly that is something you can do rather than from six or eight patients.
There is this considerable investor focus on neurotox and especially Parkinsonism. How does that factor into Carvykti's competitive positioning relative to Abecma?
We believe any potential competition is a me-too drug, and there's no differentiation in the safety profile, and let me walk you through the data, right? So in CARTITUDE-1, when we conducted the trial in 2019, we and our partner J&J did not know anything about this delayed neurotoxicity a nd the reason is because among the 74 patients we treated in Phase I, we did not observe any delayed neurotoxicity or Parkinsonism.
So when we reported data from CARTITUDE-1 at ASH 2020, we did see five cases of Parkinsonism, and then later, I think in the label, you see that there's an additional case. That case happened on day 914, nearly three years after infusion of CAR-T. Based on these findings, we at J&J immediately started to look at the root cause, and we found out a couple of risk factors.
One is high tumor burden at baseline because, as you can imagine, if a patient is heavily pretreated, they come in with a very high tumor burden. Typically, the definition for that in clinic is that if you do the bone marrow biopsy, you will see 50% or 60% or even higher proportion of cancer cells in the bone marrow.
So in that case, you do see a very fast and also very high peak T-cell expansion, which corresponds to both CRS and neurotox. So there's a simple fix that we asked the sites to use effective bridging therapy. So you can reduce the tumor burden. Therefore, you can reduce the peak T-cell expansion and also the Cmax there. W hen that happens, you will see less delayed neurotox. Second correlation is high-grade CRS.
So in our first protocol, we only recommended IL-6 or steroid use when the patient presented with grade two CRS. However, if you look at our competition, they actually started this management whenever you see the first sign of CRS. So after we instituted those two risk mitigations, in the CARTITUDE-4 trial, you can see that with those more than 200 patients, we only observed one case of very mild grade one, so 0.6% Parkinsonism.
T hen in the label, you see there's another case because there's one patient who actually progressed while we're manufacturing. So in this case, because the patient has progressive disease, you're not supposed to use CAR-T. We all know that. But unfortunately, the physician decided to use CAR-T because the patient is being progressing. So we did see another case. But again, in this case, it's a grade one downgraded to grade two.
So overall, in the label, you can see it is less than 1%, and it's all grade one mild cases of Parkinsonism. So I believe with the more use of Carvykti in the second line, you will see a pretty significant decrease in the Parkinsonism. I think the latest finding is that we also have in-house biomarker data that show that there's a direct correlation between ALC, absolute lymphocyte count, with this type of delayed neurotoxicity.
If you can manage that between day seven and day 14, when you see peak expansion, then you can actually pretty much prevent this. In fact, we believe that in the next month or so, you will see a publication at a medical meeting to show from a single center where they instituted this ALC biomarker protocol where they will treat patients with about three-day tapering course of Dexamethasone.
Before and after, you do see a pretty significant decrease in this type of delayed neurotoxicity. So we think we found the root cause, and also we found the solution. In fact, multiple clinical centers are doing this today a nd that's why we feel really confident about the safety profile here.
Okay. How should we think about revenue growth in Europe and other ex-U.S. regions?
Yeah. You probably would see that in the last year also, our revenue coming from ex-U.S. accounts for 10% or less. That is not a reflection of the demand. In fact, that is actually our decision to allocate because we launched first in the U.S., and the U.S. remains our primary area of focus of commercialization. That is why.
But with our new supply coming out from our first facility in Ghent and also by the end of this year, another much larger facility, we do expect that over the year and also next year, you will start to see more contribution from ex-U.S., especially European markets, and we do have plans to launch up to 15 markets this year outside of the U.S.
I just have a question on the follow-up on the bridging therapy. In CARTITUDE-4, did you lose anything in that process? I wanted to follow up on the bridging therapy. In CARTITUDE-4, the question is, did you lose anything by instituting bridging therapy? I'm specifically referring to in the briefing document for second- and third-line, there was an initial mortality signal.
I think it lasted for maybe six or eight months. There were about five questions in the briefing document with a number of charts. I know you answered it appropriately, and you got approved, b ut I'm curious what your answers were, and does that affect the launch at all?
N o, David, because I'll tell you why. This topic was extensively discussed during the ODAC panel. So the reason why we're seeing that, A, that reflects the sickness of this patient population we enrolled, b ecause remember, this premature death, A, does happen before Carvykti was infused. It has nothing to do with Carvykti because they didn't even see Carvykti at all.
Secondly, I think when we conducted trial, we started the trial back in 2020 a nd back then, there were certain drugs that were not approved. For example, today, you can use Talvy, which is a GPRC5D targeting bispecific as an effective bridging therapy. Back then, even Kyprolis was not approved, right, for this setting. So this is why back then our hands were tight because we did not have a good choice.
We only could use either DPD, which is Darzalex, Pomalyst, Dexamethasone, or PVD, Pomalyst, Velcade, Dexamethasone. Today, things are very different. You have two commercial CAR-Ts approved. You have three and soon to be four bispecific approved in the market a nd also, you have the Kyprolis-based regimen that's approved by the FDA.
So today, the physician would have a wealth of options that are effective to reduce tumor burden. T hat is why we believe in the real world, you will see better outcomes. In fact, like I said, this was extensively discussed during the ODAC panel. We got unanimous yes votes from every single doctor based on this.
No. We're not seeing that as a problem. Like I mentioned recently, what we're seeing is that many patients are being bridged on GPRC5D bispecific. It does not affect the BCMA efficacy, yet it's very effective in reducing tumor burden. Yeah.
There's a lot of talk around decentralized point of care manufacturing, Miltenyi and others. Do you see them as a future threat from the centralized manufacturing model, or can you just throw some light on that?
So if you look at the seven CAR-T brands that have been approved by the FDA so far since 2017, everyone used what we call centralized manufacturing. Why? Because when you have a centralized manufacturing facility like we have in Ghent or in Raritan, you have 100% control on quality a nd that is actually one very important metric.
Why? Because CAR-T, as you know, especially autologous CAR-T, it's individualized therapy. So in order to meet both EMA and FDA releasing standards, you better have very tight quality standards, right? If you have decentralized manufacturing, well, are you going to have all this quality control staff at all different sites? How do you ensure GMP?
How do you ensure you can't release every single bag according to the FDA-approved standard, right? That is probably why so far you're seeing all seven brands approved. We all use centralized manufacturing.
I think secondly, what we and our partners are doing is that because we will realize the economies of scale here, we're the only CAR-T that will, like I said, clip that 10,000 doses per year in terms of capacity and supply. So we'll realize that benefit b ut when you have decentralized, you may not be able to do this.
So question about kind of how we tie this capacity number that we talk about back to revenue, right? So if we think about the end of 2025 and this 10,000-dose capacity, how much do we have to haircut for bad batches, clinical trials, whatever's not kind of revenue-generating?
Yeah, so first, let me lay out what we have achieved to date, right? In 2023, our revenue was $133 million, and then in 2024, we tripled essentially the supply into the market because, sorry, in 2022, it was $133, and then in 2023, we tripled so that the revenue came in at $500 million.
Last year, we haven't reported the last quarter, but if you look at Street consensus number, it's about $950 million, which means essentially we achieved another doubling of our supply. Now, I can tell you responsibly here at the first or second week of January, we feel really highly confident that we can double our supply again.
That's reflected already in the Wall Street number. I think the consensus number this year is $1.9 billion, and we feel confident that we can deliver that. Now, we're not going to guide anything beyond 2025.
But what I can say is that we will achieve that 10,000, which means at a minimum, we can supply the market with 10,000 commercial slots next year a nd we don't stop there because we believe that in another two years, let's say by the end of 2027 or 2028, we should be able to eclipse 20,000 doses per year in terms of our supply and annual capacity.
Sorry. Is it 10,000 net of out-of-spec?
We're talking about commercial slots, but on the other hand, what we're seeing very encouragingly in the last year is that our out-of-spec rate has been decreasing significantly. Right now, in fact, there's a third-party survey that came out yesterday.
They surveyed 40+ physicians, and the average reported out-of-spec from the customers or physicians in this case was 10%-11%. So that gives you an idea where the out-of-spec is, and we continue to work harder, and we believe eventually we should be able to drive that below 10% and single digit.
Okay, so you're starting to talk more about the pipeline. Can you walk through what pipeline data we should expect this year?
Yeah. As I mentioned, in both U.S. IND programs, especially for the DLL3 program that's partnered with Novartis, we have treated more than, I think, 10 patients last year. So potentially, we can finish the Phase I this year. We could potentially present data at a major medical meeting for that asset.
Then the second one is Claudin 18.2. Again, we're treating patients. We're enrolling patients. So in those two sites, we could potentially have some data. Beyond that, we have a bunch of Phase I programs we're running in the IT setting in China. It includes some allogeneic programs, including Alpha Beta T program, NK program, and Gamma T program. Also, we're on track to dose our first patient in autoimmune indications this year. So these are all potentially programs that could report out.
Report out this year, or should we think of those as more like 2026?
It's not official guidance from the company, but potentially this year and then beyond.
Okay. What about cohorts E and F? When could we see those?
Yeah. I think, again, we're not guiding because according to the contract with J&J, both companies must have consistent disclosure. So historically, the policy has always been that once an abstract is officially accepted by a major medical meeting, that's when we disclose. But we do have plans to report both cohort E and F from CAR-T2 potentially in the year of 20 25.
Okay. W hat about CARTITUDE-5 and CARTITUDE-6? What's the progress we should expect on those trials this year a nd when could we see data from them?
Yeah. So let me talk about CARTITUDE-5 first. This is a randomized controlled trial comparing, again, one-time injection of Carvykti versus RVd, which is FDA-approved, gold standard in this setting for transplant-ineligible or transplant-deferred patients. So we completed all 650 global enrollments last year.
Right now, we're in the follow-up mode. If you look at our disclosure on clinicaltrials.gov, it says that primary completion for that trial is 2026. So that gives you an idea when potentially data may be out. T hen for CARTITUDE-6, which is our frontline trial, again, pitching Carvykti against transplant a nd in both arms, patients will receive also DRVd as a quad regimen. So in that trial, we are actually enrolling as we speak.
We started enrollment the year before, so in October of 2023. Right now, the enrollment is tracking above our expectations. So potentially, we could finish enrollment maybe this year even. T hen, of course, that is in the patient population who may have PFS of a few years because these are newly diagnosed patients who are also eligible for transplant.
So we have plans to sit down with regulatory authorities, including FDA, to talk about potential use of MRD inactivity as a registration endpoint for accelerated approval. You have to stay tuned. Once we have that, we'll talk about the regulatory plan.
Okay. H ow should we think about the bar that Carvykti would need to exceed to become a frontline treatment?
Sure. So let's talk about CARTITUDE-5 first. RVd, as an FDA-approved regimen, showed a PFS of about 36-40 months in two large Phase III trials. So that's the bar to beat because we're actually looking for superiority, not non-inferiority here. We feel good about that because, as you know, even in CARTITUDE-1, among the 97 patients who are heavily pretreated, literally those patients would be expected to die within 9-12 months.
Yet in that case, we have not reached median survival yet at this point. So we feel that if you look at the PFS in that trial was 35 months. T hen if you look at CARTITUDE-4 in our most recent disclosure, after about 35 months of follow-up, we have not reached median either. So we feel really good about the chance of beating that 36-40 months in frontline comparing Carvykti against RVd.
Now, in CAR-T6, because these patients are transplant-eligible, so the bar here is the trial done by our partner, J&J, for DRVd in the frontline there. The four-year PFS rate was about 85%. So that is the bar to beat.
Great. I think we're just about out of time. Any last questions in the room? Okay. Great. Thank you.
Thank you.