Okay. With that, I guess we'll get started. Good morning, everyone. My name is Noah Eisenberg. I'm a biotech research associate with JP Morgan. It is my pleasure to introduce our next company, presenting company, Autolus Therapeutics. Presenting on behalf of the company is CEO Christian Itin. After the presentation, there will be a Q&A session. Please raise your hand and a mic will be brought to you if you're in the room. You can also submit questions in the portal online. With that, I'll hand it over to Christian.
Thank you very much. Thank you very much. Welcome everybody. First off, congratulations. You made it to Thursday at the J.P. Morgan conference, that's an accomplishment in its own right. Great to see you all, and frankly, thanks for joining this late presentation in the schedule. I'll be introducing you and walking you through where we are and where we stand with our programs.
We're developing CAR T therapies and obviously, we're a listed company, and please look at our SEC filings for the risk factors that are relevant for the company. We're building an integrated CAR T company, and we're actually very much down the line in actually accomplishing this goal.
First off, our lead program, obe-cel, just read out the primary endpoint on the pivotal study, which gave us a lot of confidence around the program. I'll actually introduce you to the data that we just announced. The indication that we're active in are patients with acute lymphoblastic leukemia, a focus on the adult patient population, which obviously have a very poor outlook, and we're starting to see very remarkable data, and I'll be walking you through that.
We're also exploring the activity of the product in non-Hodgkin's indications. I'll give you a flavor of that, but I think there's significant opportunity for the program to be expanded beyond ALL into an additional indication set as we progress.
The pipeline is really built on a suite of technologies that we developed over the last few years that allow us to really tailor the properties of our products. I'll walk you through some of those technology elements because they also led to some of the deals that we have announced more recently and are relevant in that context. What is really important in our field is the ability to supply product. This is a personalized therapy.
The ability to actually deliver for every and each one of the patients is absolutely necessary and it is essential. What we've built up is a very significant level of capability. We've obviously, just as I said, completed a pivotal study. We dosed all the patients. We've done it through the pandemic. This obviously was very challenging from a supply perspective.
We managed to deliver product to all our patients, do this successfully, and navigate all the various challenges that were coming up on logistics and many other aspects. The manufacturing setup that we're using for the commercial supply of the product is coming from a manufacturing facility located in the UK. Also, our clinical trial suppliers come from the UK, and it's designed to allow us to capture about two-thirds of the total market opportunity, both in the US and in Europe. We will, out of the gate, have an ability to actually serve the market.
This is very different from what we're seeing with the CAR T programs that have fantastic data in DLBCL, fantastic data in multiple myeloma, obviously are dealing with much, much bigger indications and are really difficult to catch up on with the demand and actually fulfill the need that is currently out there. I think any one of you that actually has relatives or friends trying to get access to these therapies today do know that this is an incredibly difficult thing to do.
Many people, even as well connected as we may be in here, are not capable of getting access. We're going to be in a very, very different position because out of the gate, we'll have the capability to deliver the product at the scale required. Now, we've set up a set of collaborations.
An important one, we closed at the end of 2021 with Blackstone Life Sciences. A collaboration that includes the total value of $250 million, of which $220 million are actually already paid into the company. They were part equity and part program financing for the lead program, obe-cel. We also established technology collaborations with Moderna and BMS. I'll briefly talk about that later on as well. There's obviously quite a bit of opportunity for additional collaborations going forward. This is a business where we're at the stage where we are, where we're obviously having a readout on a pivotal study.
We're driving towards a BLA filing and have to get ready for commercialization, where you have to be able to fund your activities, so having a strong cash balance is important. We did raise some additional capital at the end of last year, as well as received a $70 million non-dilutive funding element out of the $250 collaboration with Blackstone in the same period of time.
We ended the year with about $380 million in cash, which is important. Allows us to really drive through the key regulatory steps, the filing as well as through the approval process in the U.S. and Europe. With that, I'd like to focus first on the obe-cel program. Remember, this is a program designed to see the CD19 structure on leukemias and lymphomas. This is a quick summary on some of the key features. First of all, the program actually.
Christian, I don't think we know, but your slides are not showing.
Okay. I don't think there's much I can do about that, I'm afraid. They're in display mode here.
Yeah.
I appreciate you mentioning it.
The slides are not showing.
The slides are not showing on the screens. Okay. All right. Good. Thank you. All right, thank you very much actually for pointing it out, 'cause obviously there's no visibility from where I'm sitting here or standing. The program that we're running here is really designed in a very different way from the conventional CAR T programs. What we were looking to do is create a product that engages the target cell like a normal T cell would engage it, which is relatively short, and with that, you have a high level of activity, allows the T cell to recycle quickly, and you avoid overactivation of the CAR T cells.
Consequently, you have less cytokine release, less toxicity, but you also have an ability to actually get a product that expands more in the patients and actually persists longer in those patients, which is a key feature to get to long-term remissions. What was very unusual with the program was not only that we obviously see high initial rates of activity, but we do see sustained activity in these patients.
We have now data that is going out to four years in follow-up, and we're seeing that patients are in continued complete remission without the need of any additional therapy. The reference point is that these patients normally do pass away within less than one year. This is a very unusual outcome that we're seeing and something that we couldn't actually see in our field before.
All those patients that actually have these long effects, as you can see in the middle, in the swim plot, the green lines, all of them have persisting CAR T cells up to four years. It's a very unusual property. It goes back to the fact that this product has, behaves very much like a normal T cell, and with that, actually gives us a very unusual level of activity.
When we look at the development path that we're going through, obviously, where we're looking to get preferred access to all the key regulators for the program, we have Orphan Drug Designations in Europe and the U.S., and then an RMAT designation with the FDA, a PRIME designation with EMA, and an ILAP designation with the MHRA. I mentioned the unique mechanism of action.
What's fundamentally different about our product is that it has an ability to engage rapidly with the target, which gives you specificity, but then also can disengage rapidly, which is a very unusual property to screen for, and which makes it completely different from any of the other products that actually have been developed in our space and all products that are on the market.
In fact, all commercial products are identical in their way on how they engage the target structure on CD19. This is also the reason why they do share a lot of the challenges on safety as well as some of the other challenges related to lack of persistence that we're seeing with many of the programs. We just completed the enrollment and dosing of a pivotal study. The study name is FELIX.
We conducted this study in 34 centers. 24 centers in the U.S., seven centers in the U.K., three centers in Spain. The study was conducted throughout the pandemic, which meant that obviously we did not have access to the centers. We couldn't go there. Obviously, the patient population that we're dealing with here are highly immune suppressed.
You can imagine this is about as difficult a population to work with, particularly in an environment where there is high risk of infection. Indeed, we did lose patients to COVID, as you would imagine. I'm mentioning this because normally when you develop in a patient population like this, you're all over the study. You're gonna be at the centers. You're gonna make sure you really control the study to the highest degree possible.
We find ourselves in a situation that we couldn't do any of that. That is important as we're thinking about what the data actually comes out of this study. It was a very challenging environment. It's also challenging, of course, from a logistics perspective and so on. We're able to deliver the study on time and on quality.
When we look at the overall outcome, first of all, we've presented a first look at the data, which is an interim analysis at the end of last year. We looked at the first 50 patients out of 90 patients dosed that had reached three months, at least, in terms of follow-up. What we're looking at is the overall response rate, which is based on complete remissions and so-called complete remissions with incomplete hematological recovery of CRIs.
Both of them from a leukemia perspective are patients that have no leukemia left in their bone marrow and elsewhere in their body. What we do see is that we hit an overall response rate of 70%, and we do have an excellent safety profile. Walk you through that in more detail on the next slide. What we do have here, I think, is on the right side of the slide here, some of the safety data. This data set actually was based on 92 patients, so this is a very mature data set. We have shown that, in fact, patients with high-grade cytokine release are less than 3%. Patients with high-grade neurotoxicity, all fully reversible, less than 8%.
We have less than 25% of patients have any form of neurotoxicity. A very unusual profile in this patient population. What we also did announce at the end of last year that the quality of the data triggered early a milestone from Blackstone under our agreement of $35 million.
That was triggered in the end of November, early December. One of the things that it gives us an enormous amount of confidence around the program is not only that the FELIX study actually turns out really well, but also that the data that we've been seeing across all studies conducted with the program are remarkably consistent. We go from the left-hand side, the CARPALL study was a pediatric study, so these are children. Typically, you treat them at lower tumor burden because you need to get them very early on.
The second study, the ALLCAR19 study, are adult patients that were treated in the U.K. before the pandemic. The PHOENIX1b study was the run-in into the pivotal study. That was already in the pandemic with most of the centers in the U.S. The pivotal study, obviously, with the large proportion of the centers in the U.S. What you can see is that we have a remarkable consistency around the safety profile as well as the overall activity profile.
One of the things that we did observe in the pivotal study is, this is not a surprise when you think about it, the pandemic background is, that we had more patients that had disease that had evolved from not only disease in the bone marrow, but evolved to actually take hold in other parts and other organs and successfully grow there, so-called extramedullary disease.
In fact, what's known about those patients is that they're very poorly responding to therapy. In fact, if we were to correct and just look at the patients that have no extramedullary disease, our levels of activity are absolutely smack on where ALLCAR19 was tracking before.
Gives you a sense for the robustness of the data, but also the real-world character of the data that we've actually generated here, not voluntarily, but as a matter of fact. When we then look into kind of the outcome, this is really where we have the long-term observation. This is now from the ALLCAR study where we, as I mentioned, up to four years of follow-up. This is really what makes the program very unusual.
Clinical benefit in these patients is the ability to convert patients into complete remission and sustain them over time with any additional need of therapy. You can see, we go bottom up. Obviously, we had some patients that did not respond. We had some patients that responded but relapsed quickly. The yellow circles are patients that relapsed with so-called CD19 negative disease. In essence, the leukemia became invisible to the therapy by losing the very structure the therapy was designed to recognize. If you then go a little further up, you see three red circles. Those are patients that relapsed actually because the CAR T cells, the obe-cel product, didn't persist long enough. The cells petered out, and then you actually had disease coming back that had CD19 on its surface, and the patients were relapsing.
Above those, you see a group of patients that are in long-term remission between two years and four years without any additional therapy. 35%, there is the second from the top, had a transplant, but everybody else, the seven out of 20, the 35%, had nothing else, and they're in continued remission. Every single one of these patients has persisting CAR T-cells. This is a very unusual property. You haven't seen any of that with any other program reported to date. Gives us hope that indeed we can get a transformational outcome for these patients, which frankly was the hope that we had when I developed with my old company, Blincyto, the current leading program in the space. We could never get that. This is very different.
When we look at the standard of care, I mentioned Blincyto before, which is a T-cell engaging CD19 targeting monoclonal or antibody, bispecific antibody that is being marketed by Amgen, developed, as I mentioned, by my old team when I ran Micromet, has a very attractive profile. When you look at the safety, it has a very good safety profile, similar to what I just told you that obe-cel has. The difference is neurotox of any grade in these patients is 65%. What we're seeing with obe-cel is less than 25%. This matters because you don't know when a patient has neurotoxicity, whether that patient develops a significant form of the adverse event or whether it's just a passing event. We have a remarkable outcome here compared to Blincyto.
Obviously, when it comes to efficacy, we're beating Blincyto hands down on every aspect of efficacy, most importantly in long-term outcome. Besponsa is used as a bridging therapy, can induce responses, cannot hold responses, and it's used as a bridge to transplant or a bridge to another therapy, so it could never actually get a stronghold in this indication. Then we have Kite Gilead's Tecartus program, which is the first approved product in adult ALL. As you can see, the product has a high level of activity, but it comes with a very significant level of toxicity, where you have 26% of the patients with high-grade cytokine release syndrome, 87% with neurotox, 35% with high-grade neurotox, and 40% of the patients on vasopressors.
Give or take, half of the patients end up in the ICU to be managed. That does not happen with obe-cel. When we're looking at kind of the opportunity, the medical need, actually the medical need hasn't changed much. As much as I would hope to have said that it did after we got Blincyto onto the market, we bought time with that product, but we didn't change the outcome. We still have about 3,000 patients that are in need, relapse refractory setting and stage of the disease between the U.S., Europe and Japan. When we look at the opportunities here, obviously, it's clearly the focus has to be on a therapy that gives you a long-term outcome, which is sort of the key parameter that you have to go for.
Now, in order to understand actually what that medical need is and what you can do with a program in this indication that actually is suitable for a large part of the patients, we can look at Blincyto. Blincyto will be, at the end of 2022, above $500 million in sales. When we look at the program, what that means is that approximately 2/3 of the patients do receive Blincyto today. When you look at the cost of the therapy, it's about, around $100,000 per four-week cycle. The median of the patients get about two cycles.
If you treat patients that have lower disease burden, you will be able to actually give them a third, maybe a fourth cycle of the therapy, at which point, the cost of therapy are very close to identical, actually, what we're seeing on the CAR-T side. What is important, though, in terms of what enabled Blincyto to reach that number of patients is the safety profile and the fact that the product can actually be managed, not only in an academics center, but also in non-academic hospitals. We believe with the safety profile that we have, and obviously much less complexity in delivery because it's a one-off therapy, it's not, sorry, a continuous IV infusion that you have to actually give over four-week cycles for an extended period of time with Blincyto.
We believe we're very well-positioned to actually be able to capture that opportunity with our product. In terms of price, the prices in the CAR-T space, in ALL are between about $450,000-$500,000 in the U.S. In Europe, about 10% reduction of that price. When we look at the steps forward, first of all, we're planning to have the full data at ASCO, middle of this year, also another one at the data EHA, so that's gonna be in the June timeframe. We will have long-term follow-up plan for ASH. We're targeting the BLA filing for the program towards the end of this year. The EMA, MAA filing towards the end of the first quarter 2024, and the U.K. filing in the second quarter of 2024.
That sets us up very nicely for the key territories that we expect to be initially active in. Manufacturing, obviously critical, is that your commercial manufacturing site has to be fully validated and demonstrated its full level of activity and consistency. That work is currently ongoing. The facility actually was ready at the end of last year. We could take over the first clean room, started that validation work. In the next six months to seven months, this is gonna be a key focus to get the commercial facility fully validated. This is not a nice PowerPoint slide, this is a real reality with brick-and-mortar and an actual facility. When we look into the commercial side, the critical things that we need to focus on this year, on the one hand, it's medical affairs, it's the awareness around the program. Secondly, it's the HTA dossiers.
It's the value proposition for the payers, which is really critical, to pull together. The third area is the center onboarding. Centers take about 12 months - 15 months to be ready to be able to deliver commercial CAR T product, and a lot of that time actually comes from contracting. Obviously, you have to have the product handling, the handling of the patients, but also you need reimbursement support, you need other services at the center, et cetera. It's a bespoke approach for each one of the centers and to sort of make sure the center is in a position, to actually deliver product to patients. That starts middle of this year, and obviously is a key activity to be ready.
Now, moving to sort of the broader opportunity that we see with obe-cel, we've been doing quite a bit of work, this is on the right-hand side, in non-Hodgkin's lymphoma, as well as in chronic lymphocytic leukemia. We start to see remarkable levels of metabolic CRs across the non-Hodgkin's indications. We also see very nice levels of activity in CLL, including patients, obviously reaching molecular clearance of the disease in the marrow, in all responding patients in CLL as well. The safety profile is remarkable, you know, a remarkable safety profile from CRS and ICANS perspective. I think will bode very well for this program and the positioning of this program in this phase. We're exploring the opportunities here. There's a number of options.
I think we have particularly attractive opportunities in the more aggressive forms of the disease, again, where you have a chance to get long-term remissions and transformational outcomes. In terms of the life cycle, we started to work on sort of the next version of obe-cel, which we call AUTO1/22. What we're looking to address is a problem that we picked up in the pediatric patients. Most of the kids that did relapse because they lost the CD19 structure on the surface of the leukemia. In order to make it very difficult for the leukemia cells to evade recognition, we actually engineered a second chimeric antigen receptor into our product, which is very potently recognizing and attacking cells that express CD22, so a second structure on the surface.
We tested this initially in kids that were not eligible for Kymriah, which is the standard of care. Kymriah's Novartis' CAR-T program, highly active, true standard of care now in pediatric patients. If you already had been on Kymriah and failed, you cannot go back on, at least not in the U.K. If you had extramedullary disease, you also would be excluded from getting on Kymriah. We have basically a group of patients that are true end-stage, cannot actually get access to CAR-T. When we look at the activity we would have expected for obe-cel in those kids or Kymriah, it's about 40% overall response rate. We're coming in at 83% with our product. We have a very high level of activity, very good safety profile again.
It would tease us up very nicely as sort of a part of the life cycle with the iteration of the program. We're currently looking at the timing on when to take that program into further steps, development steps, but we can choose the timing on this program to some extent. We'll balance it with an expansion of the indications for obe-cel in terms of the order at which we're gonna do that. Now, just a word on the pipeline. I mentioned the fact that we have a modular approach to sort of programming the cells, and we do that with protein modules that change the behavior of the cell. Obviously, one behavior is. One is the recognition of structures on the surface. That's the targeting element.
They're also basically the way for the cells to adapt to a difficult environment, a hostile environment. We're using, for that, modules that actually render the cells insensitive to checkpoints, an area of a lot of focus in oncology. TGF-beta is another example. Also give the cells a survival support in that hostile environment as well. Quite a bit of technology there. I do mention that not only because we introduce in our own programs, but it also has been the basis to act for the collaboration that we have on place with Moderna and with BMS, which are actually around particular aspects of the technologies that we have developed. Now, when we look at the early-stage pipeline, we got the AUTO-4 program, AUTO-5 program, targeting T-cell lymphoma.
Unique challenge, very difficult to target that lymphoma without actually rendering the cells a plastic for T-cells, which is not compatible with life, as my CSO convinces me every time when we have that conversation. When it comes to solid tumors, we're also starting our program with a very sophisticated cell programming neuroblastoma, as well as a multiple myeloma program that we currently have active with our collaborators at UCL. Now, the program in T-cell lymphoma, again, very high medical need. In fact, when you look at the NCCN guidelines, it basically says, once you're through the frontline therapy is go on, and you relapse, go on a clinical trial. That's not an endorsement of the standard of care. It's a really difficult situation.
It is a very high medical need setting, quite similar to what we're seeing in acute leukemia. What we're starting to see with AUTO4 as we're dose escalating, we're going bottom up from low doses to higher doses, we start to get these green lines again, as seen before. Those are, in fact, metabolic complete remissions. We're starting to see meaningful nine months to 12 months follow-up in these patients sustained in metabolic remissions, which is really encouraging because it tells us that we're safe, we have an ability to hit the T-cell lymphoma, and we're not actually impacting the overall T-cell compartment, which is the other part of that equation. We're currently optimizing the manufacturing process, and we're actually retesting in a few additional patients.
I think with that, we'll have a very good view of the overall profile of the program, and with that, have an ability to take it forward. The sister program, AUTO-5, is in late IND stage enabling studies. We are certainly looking at this program also as an opportunity for potentially a partnering around it. Now, manufacturing, I mentioned before, the importance obviously here is when you deliver a personalized medicine, it is personal. You have to deliver for every patient that you actually take on to your product, and you have to make sure that you can do this consistently with consistent quality, and you have to be able to match the demand as we talked about at the onset of the conversation here.
What we're looking at here in the middle is a picture of the build of the facility that was in September, where we're lifting the HVAC units on top of the facility. As an aside, this is a complete modular build-up here, fabricated to about 90% off-site. We did this whole project from breaking ground to actually taking over the first clean room in 12 months and two weeks. It's a very unusual build, and we did a modular build-up, also thinking about the potential for adding additional facilities over time in other jurisdictions. It gives us the scope, and with regards to 2,000 patients, what currently is being reached in this indication with Blincyto, about 60% of the opportunity. We believe that actually sets us up very well for a successful launch of the product.
We're in the process of manufacturing or putting together the key data for the BLA submission. The way we do manufacture is with a fully enclosed manufacturing process. We're operating with Miltenyi Prodigy machines. Been working with Miltenyi for probably close to eight years... seven years now. Are making sure that we can use as much automation as possible in the process. What this allows us to do is actually manufacture this product with a very attractive cost of goods, which has been one of the other issues that we have in the space. We expect our cost of goods to be in the range of about 15% at the as we're sort of getting this product to market. This is not only very active, but it's also economically sensible with a reasonable level of profitability.
I think that is not has been certainly a challenge across the field, so it takes a lot of attention to that particular topic, and that's what we've done. These numbers are fully loaded, by the way, with the full knowledge of the cost of the facility as well as all depreciation and so on and so forth. Just finally, obviously, we've added quite a bit of cash towards the end of last year. We did a public offering, had some cash coming back from the tax services in the U.K., also $70 million from two milestones received from Blackstone.
One was obviously related to the achievement of the pivotal study endpoints. The second one was actually related to manufacturing progress, which is very critical as we just went through, and got triggered by key data that we generated in that process. Finally, obviously we think we have an interesting year ahead of us. Obviously, focus is really to get obe-cel into the regulatory process, with key data releases planned for middle of the year as well as the end of the year. Filing, first filing towards the end of the year, and then additional filings in Europe in the first half of next year.
We expect to provide updates on the pipeline programs with additional data and follow up, obviously have quite a bit of opportunity to sort of actually continue in our collab ability and our set up for collaborations as well. I do mention the manufacturing topics as well, and getting ready for the commercialization. With that, I think we're in a very interesting point with the company. We got the cash to deliver a very significant value step. We got the data to know that we have a differentiated profile of a product that addresses a high medical need with limited competition and with possibly a transformational outcome. With that, happy to take questions. Thank you.
Great. Thank you. Just as a reminder, there will be mics around the room, and you can also submit questions via the portal. To start, you mentioned that in the FELIX study there was a disproportionate amount of enrollment of patients with extramedullary disease. What makes these patients less likely to respond to therapy?
In essence. First of all, it's a higher amount of those patients, not disproportionate, because that would suggest it's like half. That's not what it is. It's a substantial amount of the patients. What makes the disease more difficult to treat is that it's basically an evolution of the disease, and you can think of it as like a gain of function, 'cause the normal location for this disease is in the bone marrow. That's where the cells reside, that's where they grow, that's where they outcompete and frankly, you know, inhibit the activity of the immune system to regenerate in the marrow. With that gain of function, the cells actually change in terms of the phenotype. They're able to migrate to other places in the body and then grow.
In that other environment, not in the bone marrow, the cells are more difficult to get to, and because they've basically learned a few more tricks, actually are more difficult to handle. Typically, what we're seeing across the board is about a 50% reduction in overall response rates in patients that have extramedullary disease. It's a real kinda challenge to actually tackle those, that stage of disease.
What is the background rate of patients with extramedullary disease?
It's relatively low, and it's. In a way you can think about it's you select out these patients because either if you have a very rapidly progressing disease, and you don't have much intervention, the patient basically dies, typically, of infection, often sepsis. Obviously the more you can basically keep the patient alive, you start selecting out more advanced stages of the disease, and that's basically what we're starting to pick up. It's been reported as an example, as a challenge for patients that have been on Blincyto, and many of the patients post Blincyto do actually relapse with extramedullary disease, and that's been a huge issue for the physicians to sort of handle the patients at that stage.
Hi. Congrats on the data.
Thank you.
One of your slides mentioned, for partner for commercialization of obe-cel, you're considering EU partnering. Could you speak a bit more to that and what commercialization activities you're planning to do yourself versus partnering?
On the commercial side, the current focus that we have, primary focus, is to commercialize the product in the U.S. We're setting ourselves up to be in a position to commercialize in Europe, but I think we're open to consider partnership in Europe. Obviously, we're supplying the product, but we would definitely be open for a conversation. This has a lot to do with just managing complexity. As we're sort of going through the process, as you can imagine, there's a lot of heavy lifting as you're setting up the infrastructure for this type of a therapy, in that regard, I think that's certainly a conversation that we can have.
Okay. What feedback have you gotten from physicians regarding the CRS and ICANS, in their decision to employ CAR T over other options in ALL?
Well, it starts with the I think the realization that there unfortunately for these patients, you're pretty much out of options. You can put them on Blincyto, they will fail eventually. At that point, you're typically very close to palliative care. In fact, today you could use Tecartus still in these patients, but because they're very frail, that's not an easy decision, particularly if you see the adverse event profile and the limited long-term benefit that, you know, I think so far has been established. It's a very difficult environment, I think, there, and there's a very high medical need. Having a product, particularly in these patients that are not doing well, that is well manageable, is really important.
Obviously from an overall perspective, actually having a chance of a long-term outcome is all you'll be looking for at that stage. Clearly, putting the program into an earlier line, which is activities that we're active in, including treating patients with minimal residual disease, that is obviously the optimal place to actually place the product, and that's how you will maximize positive outcomes for patients. Unfortunately, there is not an awful lot of options left at that point. These patients tend to have gone through stem cell transplant, failed many of them. Those that didn't get a stem cell transplant actually were not in a position to actually take one because of the toxicity. Getting a second transplant that has sort of a treatment-related mortality, that's up to 40%. It's a very, very difficult choice.
Europe typically isn't done, but also in the U.S. mostly isn't done.
You just meant... You're enrolling both a morphological and an MRD cohort with obe-cel. Could you just give us some color behind the strategic rationale of the MRD cohort?
Right.
Mm-hmm.
Happy to do that. One of the challenges we have in the field is that the regulators require us, at this point still, to actually wait for patients to have a certain amount of disease burden in the marrow before you can actually include them in the trial. This is called morphological disease. It requires you to have 5% disease burden in the marrow. The reality is that we all know in the field is that these cells all come from a single clone, and that's just a single cell growing, growing further. The field has, over the last 25 years, developed obviously methodologies to actually pick up a clone that starts to grow very, very early. That's initially done by flow cytometry, then was done by PCR. Now it's done by NGS, by sequencing.
The sensitivity instead of 5% is one in 1,000, one in 10,000, one in 100,000. When, as a physician, you see that signal come up, that's the point where you actually start treating. You do not wait till that patient gets worse and has 5% tumor burden before you start treating. What we have is sort of a situation where we have a disconnect between what's required to get regulatory approval and what clinical practice is. What we're looking to do is that we're generating data to actually also support the physicians in their own decision-making to actually utilize the product at a lower level of disease burden, which is frankly the right thing to do, and it's straight rational when you think about what the disease is, how it works.
When you look at, in particular, the pediatric situation, where the disease is also quite explosive in its growth, is that there was an approval for Kymriah in morphological disease. Today, the physicians are treating the kids ALL when they actually are in MRD, minimal residual disease, low tumor burden, 'cause it gives you more time to actually fight the disease, and it gives you a much better chance to win because there are less cells to get rid of. It's a probability game. The more cells you have to get rid of, the more likely it is you're gonna miss the one that ultimately will kill you. That's really what this is about.
What we're doing with that additional work is to actually make sure there is data to support the use at a somewhat earlier stage.
Mm-hmm.
Of the recurrence.
From the regulatory feedback you're getting, is there potential to include the MRD patient data in a product label?
I think there is probably one downstream. I mean, it took quite a bit of time. We developed this strategy when we developed Blincyto, and it took quite an extensive amount of time for that knowledge to be actually included in the, into the label. A bit quicker in Europe, actually, than it was in the U.S. What we want to do is here is really provide the information for the physicians to actually make their decisions. Then obviously downstream, we expect to actually use this kind of an approach in an earlier line of therapy where this is gonna be particularly important.
Could you give an enrollment update on the MRD cohort?
I think we're just about being cut.
Oh.
Are we out?