Autolus Therapeutics plc (AUTL) Earnings Call Transcript & Summary

Good morning, everyone here in San Diego and to those on our webcast. Welcome to Autolus Therapeutics Analyst and Investor Meeting to discuss the data that we presented yesterday here at the ASH Symposium. I'm Rob Dolski, CFO of Autolus. With me today are Dr. Christian Itin, our Chief Executive Officer; and Professor Claire Roddie; Associate Professor Hematology and honorary consultant hematologist Cancer Institute, University College London. As a reminder, before we begin, I just want to remind that during today's meeting, we will make statements related to our business that are forward-looking under federal securities laws and safe harbor provisions of the Private Securities and Litigation Reform Act of 1995. These include, but are not limited to, statements regarding the status of clinical trials, development or regulatory time lines and expectations regarding our runway, our cash runway. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect only our views as of today. And we assume no obligation to update any such forward-looking statements. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to yesterday's press release announcing the ASH data and our SEC filings, both available on our investor website. On Slide 3, you'll see the agenda for today, Christian will begin with a brief intro and then we'll pass to Dr. Roddie to summarize the obe-cel FELIX data that were presented in an oral presentation yesterday. Christian will follow up with the pooled analysis from the ALLCAR19 and FELIX Ib studies, as well as initial data from the AUTO8 study also presented yesterday. We'll wrap up with upcoming milestones and closing remarks. After that, we'll welcome your questions. We're going to start with questions from the room, and then we'll open those up to questions on the webcast as well. So I'll now turn things over to Christian.

Well, good morning, everybody. Fantastic to see you all here on a sunny morning in San Diego and particular on the Sunday morning of the conference. I know many of you had already a lot of engagements on Friday and Saturday and some of you may have had long nights already on Saturday night. So the fact that you're actually showing up at 8:00 this morning is fantastic, and we really do appreciate it. I think we have a great opportunity today to actually walk you through the data in sort of a more measured pace than the typical format that we have at the conference, and it's fantastic to actually have Claire Roddie here who's been instrumental in the program -- in the obe-cel program, not only with the FELIX study, but also with the [ SENTINEL ] study, the ALLCAR19 study, and she'll talk about the update from both studies in this morning's session. One of the remarkable things about this field is that it's the collaboration that we have between the treating physicians and the companies tend to be very tight, probably tighter than you have in many of the other indication sets. We had this opportunity, my old team when we developed [indiscernible], where we had this very close relationship with universities in Germany as well as MD Anderson, and we now obviously have, with obe-cel, had this enormously fruitful relationship with UCL over many, many years, obviously, anchored with Martin Pule, our Chief Scientist, who has a dual role, both at the company as well as the university. And obviously, the colleagues that Martin obviously assembled around himself, which is a quite an eclectic group and Claire obviously, has been clearly one of the key drivers of this program and fantastic to have you here today. So just as a brief introduction, obviously, we have yesterday presented on two of our programs. The first, obviously, on obe-cel itself with an updating analysis of the FELIX study, the pivotal study. And what we've done with this study is actually pooled all the data that we had from that program, which is different from what we have presented at ASCO, where we only looked at the morphological cohort. The reason why we're looking at a pooled data set and the entirety of the range of patients is that, that's actually reflective of the reality of what a physician will actually see in terms of the patients that are coming through the door. You have patients that have very low disease burden, you have patients that have extremely high disease burden, you may have patients that actually have disease that actually does not only originate in the bone marrow, but already has gone to another organ and actually form so-called extramedullary disease, patients that actually typically are excluded from clinical trials. We had a specific cohort where we included those patients. And it is that view across this entire range of patients, which is really where we believe the real value of this study ultimately is to physicians. Because they can recognize their patients within the population of the patients that we're seeing. So we're excited to hear more about that from Claire today. The second aspect was a poster presentation. And what we were looking to do is pull together the ALLCAR19 study together with the data from the FELIX Ib study, which gives us a median follow-up in these patients of 3 years, and in fact, all the way out to 5 years of follow-up. And that starts to give us a very interesting view on where we think the actual benefit -- ultimate benefit for obe-cel will be as a standalone agent. Not as an agent that gets consolidated or it gets in combination, but as a stand-alone agent. And I think what you'll see from the data, as Claire will go through it, is there is a remarkable overlap between these data sets, and that gives us the confidence we have in our program. The third presentation that we gave was an oral presentation, Lydia Lee gave also from UCLH on a dual targeting program that targets BCMA and CD19 that was highly optimized for the use in multiple myeloma and obviously also could be used in additional indications that I'll sort of talk about, a little later. What we also will have tomorrow is a data set that we actually look at the manufacturing performance around obe-cel. And that manufacturing in performance is really important. But we're running clinical app boards now. There's a lot of that activity ongoing. This is also why we only have part of the team here today with a lot of other activities ongoing. But the first feedback we get actually from physicians is, can we get access to product. That is being one of the real challenges that we have seen in the field is that we had, on the one hand, fantastic clinical data on programs, but then virtually no ability to get your hands on the product and your patients on the product. So that is really important. This is going to be a focus on the presentation tomorrow night, which I would encourage you to have a look at because you'll get a sense for the robustness and the capability on delivery. And then obviously, very recently, we did announce that we did, based on the FELIX study, filed for a BLA with the U.S. FDA. Just as a reminder, before we go into the presentation from Claire, just a reminder of where obe-cel comes from and what we were looking to address with the product. What we did realize in the early programs that were in the spaces that they had a behavior that was not physiological. And it was a behavior that actually led the cells to attack the target cells, deliver the kill but then getting stuck on the target cells. The cells could not associate easily, and that had a very significant impact in at least 2 different directions. One is, the cells actually got overactivated because of the very continuous cell-cell contact. And that overactivation actually striving cytokine release, and it drives a lot of the immunological toxicity that we're seeing with these programs. The second aspect is that it also actually slow stand the activity because the T-cells cannot recycle and do another kill, they get actually held back. And so when we're looking at the behavior, what we postulated is that the product that would give you that level of sensitivity in terms of seeing and recognizing the target, but have then an ability to dissociate rapidly after delivering the kill, we would actually get a product that would actually have a higher level of activity. More CAR-T cells formed in vivo, better persistence and a better safety profile. That was the [ postulate ]. And this is really what was at the foundation of obe-cel. So the product has a unique property in its finding. It has an ability to fast -- with the fast binding to the target antigen. But then also an ability to actually dissociate rapidly as a fast offering. And that biophysical behavior is really what's fundamentally different about this product and at the core of the differentiation that we see in the clinical experience. So with that, it's my pleasure to introduce and obviously ask Claire Roddie up here for the presentation. Obviously, Claire's been instrumental in many of the studies that we've been engaged in. And one of the things that's really remarkable about Claire is that she did not only actually treat the patients, but on the ALLCAR study, she also manufactured the product for the patient. So see as the level of understanding of this field like very few people do, and it's a pleasure to have you here today. Thank you, Claire.

Thank you very much Christian, very generous introduction. So let's move into the data. First of all, so this is the FELIX pooled analysis. And yes, we're looking at basically obe-cel for relapse and refractory acute and lymphoplastic leukemia in adults in the FELIX phase Ib/2 study. And the question is nicely illustrated what obe-cel is. It's got this fast off with binding domain, which was specifically selected with the objective of reducing toxicity and improving persistence of the CAR-T products. And it's alluded to the fact that we have tested this in pediatric and adult B-ALL in Phase I setting. We've also has tested and primary CNS lymphoma. -- always had a wide sort of range of different applications in the Phase I setting [indiscernible]. And we're presenting initially these results from the FELIX Phase Ib/II study as opposed analysis of all of the patients that are treated to date with obe-cel including patients with low leukemia burden treatment. And what that means or how that's defined is more of the logic remission. That's less than 5% bone narrow blasts without extramedullary disease and as measured at screening and lymphodepletion. And this is the study design, which you will probably all be familiar with. There is a leukemia burden-adjusted split dosing schedule here. And I think what you can see is the fact that we do our bone marrow aspiration at screening, before we recruit the patients into the study. And then importantly, we repeat the bone marrow prior to lymphodepletion. And the reason that we do this is because we use a disease burden based titration of the initial dose of CAR-T cells given to the patient, and we use to stay minus 6 [ marrow ] to guide that decision making. And you can see that the doses are split over day 1 and day 10. And here's where the decision rests. So if you've got bone marrow blasts of less than 20% on that day minus 6 [ marrow ] , then you will receive a higher initial dose of CAR-T cells. That's 100 million cells. If you've got more disease and the perception being that, that might portend to more in the way of immunotoxicity and side effects, you then get a lower initial starting dose of 10 million cells. These patients are all followed up, and we look at it for signs of the minor toxicity. But in the absence of significant immunotoxicity, we can then go on [indiscernible] top-up dose and to reach a total dose of 410 million cells. So that's the kind of broad study schema. And the efficacy and safety follow up the first analysis point for the impact of the day 28. And in terms of the patient eligibility and endpoints, as you can see, we've split this study design into 3 main cohorts. You've got cohort A, where we've got morphologic disease that's more than 5% bone narrow blasts at screening. You've got Cohort B, whether it's MRD-level disease, up screening that is MRD positivity, but less than 5% blasts and cohort C is where we're treating isolated extramedullary disease. And then I think you can see here, I'm seeing our CRI rate and duration of response, EFS and OS, and of course, importantly, MRD negativity, safety and feasibility. So in terms of the patient disposition, 127 of 153 enrolled patients actually went on to receive obe-cel that is 83% of patients. And the table on the right-hand side of the slide illustrates reasons why patients may have discontinued and not received their infusion. The predominant reason here was [indiscernible] from progressive disease, and we know with acute lymphoblastic leukemia, the burdened infections that complicate bridging therapies and alternate strategies can be quite high. So that was the predominant reason for discontinuation. There were a few manufacturing-related reasons also and very [ attritional ] other reasons such as Physician decision. Sorry, and we'll just go back to that just to illustrate the point that in terms of the patients treated in the study, the majority of patients infused for in Cohort A that was 84% of both the patients infused, 10% were infused with Cohort B, the MRD cohort only 6% and on the extramedullary disease cohorts. So in terms of the baseline characteristics, again, it's quite a detailed slide. The minimum age of the infused patients here was 47. You can see that we actually treated one patient whose 81 years old. So again, the sort of safety profile of obe-cel coming into its own in there. In terms of the nature of the patients, they were certainly very heavily pretreated. And you can see that there is a median of [indiscernible] line and 35%. Most of the patients have had a prior allogeneic stem cell transplants and must have been exposed to [indiscernible]. And in terms of the disease burden, this is screening. The median bone marrow blasts percentage was 36%, with a significant number of patients whose disease burden was up 100% and there is a significant number of patients who have extramedullary disease, and this is a particularly [indiscernible] of patients And you can see there that, that was affected 23% of the total population. Now with this in mind and the fact that you've got this heavily in disease burden patient group, it was actually a little more remarkable, I guess, that the manufacturing was a straightforward and robust as it turned out to be. And the starting material, as you can see on the left hand side of this slide, the CD3 T-cell and presence in the leukapheresis was fairly small. Majority of patients of the total sort of leukophoresis that arrived in the lab. But despite that, the majority of patients and received a released product. And the [indiscernible] here is supposed to tell us a bit about the CAR expression in the cells. And you can see it's really pretty consistent and tight in around sort of 70%. And of course, importantly, the viability of the cells after all was really nice and high up at 90%. And a lot of the physicians who ask sort of their biggest request to us is to get a product to their patients quickly. And I think that was really nicely realized here, we can see the median the [indiscernible] time here was 22 days. So I think the point to make here is that there was really consistent manufacturing despite the leukapheresis from these patients with not only really heavily pretreated, many of whom who have analogeneic stem cell transplant, also they have a lot of disease, meaning that these factors conventionally make it difficult to manufacture for patients. So then let's look at the remission rates and the depth of those remissions. So we saw high MRD-negative remission rates across this study after infusion of obe-cel and of all the 127 treated patients here with splited into morphologic disease versus new morphologic disease. And of the 98 patients who are in the morphologic disease bracket, 74% of them have a CR or CRI and 95% of those you were evaluated for a response were MRD negative. And in the new morphologic disease cohort, that was a smaller number of patients, 29, about 100% of evaluable patients were MRD negative and when they were evaluated [indiscernible] 28. So again, good response is seen in both of those cohorts. And then in terms of the CR/CRI subgroup analysis, essentially, we're looking here at a forest plot and briefing at the different subgroups treated with obe-cel. And I think we can agree that there are high CR/CRI rates just across all of the subgroups. In particular, I think, we can illustrate the fact that the Philadelphia positive and patients seem to be doing well, even those patients who have had a prior allogeneic stem cell transplant, we might be concerned that the sorts of patients -- we've not necessarily do so well with the ALLCAR, but in this case, we're seeing really good responses. I think higher risk groups, and I think we can expect this from the data, not just from our own study, but also from ZUMA-3 is a patient with very high disease burden. And by that, I mean more than 75% plus. It is a more difficult task to get these patients into deep remissions, but they represent a sort of a small number. And the extramedullary disease again, illustrates the fact this is actually a high-risk group. And again, they are a higher risk group for CAR T-cell therapy also. So if we look at the EFS in all treated patients, well, the 12-month estimate of event [indiscernible] here was 50%. And you can see this is nice in terms of this curve. There are patients dropping off, but there is reaching a plateau. And the median followed uptime for this whole patient group was 16.6 months, but we've actually got patients as far out as 36.6 months. So we've got that nice durable and long-term follow-up for some of these patients. Only 17% of the patients, the responders proceeded to stem cell transplant in remission. And again, that's informed [indiscernible] in some of the other CAR T-cell studies where physicians prefer to consolidate their patients' remissions with a transplant. And I think because it's the durable persistence of the CAR T product on this trial, I think there were less patients that were referred on for this therapy. Then in terms of the obe-cel persistence and responders, I think we can agree, this looks quite familiar to us. This is a bit like what we saw in the Phase I study. We've got this really nice look -- this nice high initial expansion here, and this is sort of our target of 100,000 copies or microgram of genomic DNA. That's when we look for the CAR by a DNA measure in the peripheral blood of these patients. And a nice peak is happening sort of within the first 28 days before day 14, really. But I think what's really nice here is the fact that the persistence is actually plateauing at around [indiscernible] copies [indiscernible] genomic DNA. So we have got that persistent signal in our responding patients that lost follow-up. And in fact, CAR T persistence was detected in 72% of ongoing responders at last follow-up in this cohort. Now this slide is basically to illustrate why we do the bone marrow aspiration prior to lymphodepletion because, of course, we're making an important clinical decision at that point. We've decided we want to stratify patients first to supporting to their disease burden. So what this is trying to illustrate to us is that -- you cannot predict disease burden at the point of screening on this study. So you'll see here that we got the patients here at screening. This is the bone marrow blast percentage, and this is a lymphodepletion. And 93% of our patients receive bridging therapy and certainly response to bridging was not universally successful. And I think if you follow these lines out, you can see that a proportion of the 5% patients with 5% or less disease, they stayed at that level, but there were a number that went on to develop sort of this intermediate level disease, that's between 5% and 75% and the way in a proportion that ended up with more than 75% blasts. So again, would be making the roaming decision to use this marrow as a result to guide to the first [indiscernible] study. And we can sort of see similar patents really in this intermediate group between 5% and 75%. We see a proportion respond to bridging and go to less than 5%, a significant number stay right where they are. But you can also see some of them refiling into this very high risk was more than 75% blasts. But interestingly, even with these patients with lots of disease at screening, you can see that sets of them are pretty refractory to bridging therapy and they remain at 75% at this point of lymphodepletion with some bridging therapies, we do have success in reducing burden. And so for instance, proportion here are going into this intermediate bucket and a proportion can go into less than 5% blast. And anecdotally, there are some success stories with inotuzumab being used as a bridge, one can achieve deep but transient remissions and good disease [indiscernible] with the judicious use of that agent. So I think the point to make here is that the sort of the pre-lymphodepletion is really important in terms of determining what treatment we give to our patients. And again, let's talk about this leukemia burden associated with the EFS. I think we maybe didn't dwell on this in lots of detail in yesterday's presentation, but it's important to look at these lines, maybe sort of in a bit more detail. So this blue line at the top of the graph, these are the patients who had 5% or less blasts at the point of lymphodepletion, this green ring is telling us about the intermediate cohort, that's between 5% and 75%. And then we've got this line at the bottom here, which is telling us the patients with 75% or more percent blasts in the bone marrow at lymphodepletion. I mean it's really striking, isn't it? The difference between these curves. And in fact, it was also some [indiscernible] for long-term EFS, if you have well-controlled disease at the point at which you come in for obe-cel. But actually, this sort of 5% to 75%. The pattern is the same. You're getting this nice plateau coming off both of these curves. So these are not dissimilar, but there is something about having more than 75% blast biologically that is difficult to deal with it. Presumably, it's just -- this is worst prognosis disease, and it's a harder nut to crack, if you will. And I think -- I think you can see that this is reflected even in the numbers at the bottom of the Slide, if you look at the 6-month EFS and we look at our less than 5% blasts, you can see that the -- and the 6-month EFS here is 83%. But if you follow that across to those patients with more than 75% blast, you can see that drop to 40%. Again, this isn't really a surprise to us. This is exactly the same pattern that we saw on ZUMA-3 and this is -- it just represents a particularly difficult patient population to deal with. And I think the way that we move forward with this sort of thing is to try and figure out how we can reduce these disease burdens down prior to giving CAR T-cell therapy. And again, let's talk a little bit about toxicity because I think this is the piece that really emphasizes the differences with obe-cel compared to other products. So there were really low rates of Grade 3 or more CRS and icons on this study. You can see on the left hand side of the slide here, this is the overall patient population. 69% overall CRS, 23% overall ICANS, but very low rates in the dark grey here of weak 3 or more events than 2% CRS and 7% ICANS. And of course, we then take that 1 step further and stratify that according to bone marrow blast percentage of lymphodepletion, where you can see exactly how this turns out. It is from a disease burden that portends to give immunotoxicity look a bit over 75% blast, representing the majority of the immunotoxic events in terms of CRS, but particularly in terms of icons here. You can see that the over 75% had 15% ICANS represented as a proportion of the total. And whilst this -- as a clinician, we don't like merging Grade 3 events, I mean this is not dissimilar to the data that we've seen with the TOWER study and the use of blinatumomab. So within [indiscernible] pool, we have to emphasize the fact that the toxicity profile here really is sort of almost best in class. And I think the other thing to note is that if we can control patients' disease, we're getting no grade 3 CRS, no Grade 3 ICANS. This really does truly represent the kind of agent would be safe to give in the outpatient setting. I think that's sort of like a flavor that we have amongst the clinical community at least in terms of where obe-cel sits, and that's in the patients with less than 5% blasts at lymphodepletion. So I think that's a really sort of exciting direction of travel for us. Now in terms of the patients that got CRS, there was a very few things that have sort of severe phenotypes that require vasopressors. That was only in 2.4% of the patients. And again, that -- I mean, it sort of stands up really when we compare it to our closest sort of competitor again with Tecartus where there was a significant use of vasopressors and in those studies. So concluding I think that's a really important point that obe-cel will successfully manufactured for so many patients, 95% of leukapheresed patients got a product, and that's despite the really low CD3 percentage and not starting material, those heavily pretreated patients. So I think that's a real sort of victory for the trial. There were high remission rates, which appear to be independent of leukemia burden at lymphodepletion. So since you can still achieve a remission irrespective of how you come into the trial. And the 50% EFS estimate at 12 months, again, is -- it's just reflecting what we saw in ALLCAR19. So it's giving us that confidence that what we saw in the Phase I is really drawing out into the Phase II experience. And that is reflected in the fact that only sort of 17% of responders proceeded to stem cell transplant while in remission. So if we follow out that EFS curve, we're actually seeing the impact of obe-cel as a stand-alone therapy, and we're not sort of seeing the [indiscernible] by the presence of [indiscernible]. On the result. Again, a very favorable safety profile here and 2% Grade 3 or more CRS and 7% Grade 3 ICANS. So against severe toxicity, as we saw in the previous Slide, it's mostly in those patients with high leukemia burden more than 75% blast. So again, it gives us a field for what patients we will be watching a bit more [indiscernible] and following infusion. And there are durable remission rates and on toxicity. But again, they tend to inversely correlate with leukemia burden at lymphodepletion. And so I think we'd emphasize again how important that is to assess the leukemia burden out lymphodepletion in order that we accurately sort of risk-benefit stratify our patient cohort. So in conclusion, I'd say obe-cel is an effective treatment, the relapse and refractory adult B-ALL, there are better outcomes observed in patients with low leukemia burden at lymphodepletion. Of course, as we always have that [indiscernible] longer follow-up is required, we want to follow these patients out, make sure these responses continue to be durable and patients continue to do well. But so far, it's really exciting data, and it's fantastic for us clinicians in the ALL space. And this is just a Slide to emphasize the TEAE [indiscernible] study, and I think that just again fits in -- ties in with the immunotoxicity side, favorable safety profile. And only 15% of the patients were admitted to the ICU, which again can [indiscernible] favorably with other agents used in the space, and there were only 2 deaths on the study that were considered related to the therapy, and that was [indiscernible] and in case of ARDS and ICANS. So again, that's quite remarkable considering the numbers of patients treated. And of course, I mean, [indiscernible] without our patients. They've been fantastic. They're all sort of warriors and the they're [indiscernible], their families and friends, and of course, all the Autolus study investigators old staff has helped to carry this off and deliver this study. So I think that we'll move quickly into the long-term follow-up in the B-ALL. Again, we've got this pooled analysis from the ALLCAR19 and the Phase Ib FELIX studies in B-ALL. So moving into that, I mean, some of this is reprising what we've already discussed. And again, both of these studies are looking at adult acute lymphoplastic leukemia, one was Phase I and one was Phase Ib. And essentially, we've got nice follow-up to talk about now. So we're reporting the long term obe-cel data. So the pooled analysis again of ALLCAR and FELIX Ib patients. And we'll also briefly mention the ALLCAR19 extension phase, which we extended out to include patients with non-Hodgkin's symphoma and relapsed and refractory CLL. So this EFS and OS curve here, this is supposed to show us the median follow-up -- long-term follow-up in relapsed refractory in B-ALL in that shared cohort that ALLCAR19 and FELIX Ib. And I think the point again to emphasize here, and the holy grail was always set out by the Eliana study in pediatrics and young adults, where [indiscernible] showed the fact that there was a plateau. Because everyone is seeking out the plateau in the EFS curve. And as far as I'm aware in the adult space, no one else assumed this, but I think we can confidently say that all this ALLCAR19 and FELIX Ib study, we are seeing a plateau in our patients. So when you get to a certain point, the relapse has stopped happening. And it's exactly the same with the OS, we're getting that nice plateau. So whilst there are some events happening up until about to the [indiscernible]. And so when you then see in the sort of stabilization of the plot. And this is just telling us that potentially obe-cel could represent standalone and long-term solution for some cases of adult ALL. If we want to talk about the numbers specifically. So there's a sensoring end points being made here. So we're talking about EFS sensor that stem cell transplant for new treatments and EFS with new sensoring, and so when we sort of take the stem cell transplant site, we can see EFS sits here, just around sort of -- you can see up here, it's sort of 45% and without sensoring, and it's 36%. But I think what we can agree is the fact that we plateaued out really nicely here. And in terms of the 26-month overall survival rate, again, that's top numbers here, that's 41%. And again, we just don't have other therapies that can deliver these sorts of results in these sorts of really high-risk patients. So again, this is a really encouraging data for us. If you want to look at the individual patient [indiscernible], the [indiscernible] plots often a good place to look. And I think the point I'd make about this is the fact that with [indiscernible] patients up to 60, as this sort of 5-year data and a lot of these patients actually come through my clinic. And it's great to see them coming in ongoing for T-cell persistence in the [indiscernible] and doing really well. So I think this is really sort of -- it's heartening for the clinical team to see these patients coming into clinic, but the point is this can represent a long-term solution for basis of B-ALL. And in terms of the toxicity, again, we're no new safety signals, no Grade 3 or more CRS. And we know about the ICANS signal from the early days, 4 out of 36, got a Grade 3 events, but they certainly [indiscernible] infective signals. And so went to pose any concerns in this patient population. And on the prolonged persistence we talked about with this product that was seen in most of the long-term responders here. And you can see the ongoing CAR T-cell persistence post this large number of patients, so it was [ 16.6% ] at 12 months and 55.1% to 24 months is pretty; comparable to persistence of 12 months, and that persistence is ongoing at 24 months. And we believe with this product, the persistence is important to ongoing maintenance of response. So there is a bit here, I think, for Christian to talk about.

Thanks, Claire. Fantastic presentation. I hope that the added color, I think, has been helpful because the challenge in attendant presentation is it's basically boom, boom, boom and there is really not much time for nuance, but I think particularly the view that actually looks what the patients look like at screening versus at lymphodepletion, that's really important. And they did resonate actually also yesterday, for those of you who were in the presentation did resonate with the treating physicians in the room, because it's something they know, but it's normally not actually evaluated or looked at systematically in the trial. And we looked at it systematically because we made our dose -- this dosing decision dependent on it. And that's one of the great outcomes of the study. It's actually beyond just the study itself, I think, has actually much more ramifications for the actual way in how we manage these patients going forward. So what I'd like to do now is just really take a brief outlook for the program into indications beyond ALL. But before we get there, just a brief reminder where we are on the journey with regards to obe-cel, we obviously filed the BLA. That is -- obviously it was an important step. We expect to file MAA with the European agency during the first quarter of next year. And then obviously, we'll really be very busy, particularly [indiscernible] team and our manufacturing team dealing with all the information requests that will come from the various agencies during the review process. So that's going to be the primary focus for the team because obviously, a lot of activity is ongoing on the commercial side. There's an enormous activity ongoing to get the clinical centers ready for the use of obe-cel once the product gets approved. That is a massive push and we're aiming to have at least 30 centers open and available at the time of an approval for the product. So this is going to be a very aggressive push, and we're going to go from there very quickly towards approximately 60 centers that will allow us to capture most of the patients and reach most of the patients in the U.S. in that process. So with that, just a few words on SLE. For those of you who were yesterday in the session where Claire presented, there was a fantastic presentation from the University of [indiscernible]. Dr Fabian Miller presented. He's part of the team from [indiscernible] University, and the data is really remarkable because they have now up to 3 years of follow-up on their patients. They see that they can reset the disease, which is a hypothesis that's been in the field for about 30 years. Resetting the B-cell compartment is an old idea. It was tested initially with rituximab, didn't quite work. So one of the key collaborators we're working with also UCL on the SLE side, actually was part of the original study that evaluated rituximab in SLE patients in the around year 2000 to 2002. So the idea has been out there, but we couldn't quite reach the depth into the compartment, particularly we couldn't reach the CD20-targeting agents, the plasma cells that are producing the autoantibodies. And the really remarkable finding from the team and [indiscernible] and actually is that the plasma cells that are reducing the autoreactive antibodies are CD19 positive. That's something we actually did not know. That is something we learned from that clinical experiment. So it's a quite remarkable outcome. Now what we've seen yesterday is obviously a remarkable reset of the disease scores. These patients go to baseline. We've seen in part actually with energies of kind of what these patients look like before and after treatment. But we didn't see, but actually are published in part are actually the CP scans on these patients where you can see fibrosis in their organs before and fibrosis gone after therapy. And that is really important that you heard in the talk yesterday that these patients had typically 1 or 2 organs involved already at the stage of inclusion in this study. So we believe we're in a remarkably good spot. Why do we believe that? The product that was used in [indiscernible] is actually a product that is very similar to KYMRIAH. It's the same fundamental receptor as a manufacturing process closer to the way we manufacture and the product was initially used in pediatric ALL patients with very similar data as we have shown in our original [ ALLCAR ] study. What's important to know about that product is it's a product with a long persistence in pediatric ALL. So this is the nature of the product. That product is what they use then in the SLE setting. And they created and really showed these remarkable data either. So this is the data from a long resistant CAR T in SLE. So we believe we're in a great spot because, obviously, you've seen from Claire that we have an exceptional safety profile or exceptional activity profile. And what's going to be very important in that space is you have to be able to deliver product at scale and economically. And that is obviously one of the core focus for us over the last few years to actually establish this capability. And I think that will become a very important part. In addition, we're obviously using the product that we already have experience in oncology and in autoimmune. So we have a known entity. We also have a lot of safety information and we will be able to leveraging, obviously, the regulatory filing. And by the time we move into a pivotal study, hopefully, approval -- approved product for -- with regards to obe-cel. So that puts us in a very, very strong position, even different from the large pharma companies who move in with new products into the automine space. They're not using their oncology products for that. So this is just a brief outlook. We're starting a Phase I study early next year, expect the first patients to be dosed in the first part of next year. So that we should actually have data to guide us with regards to the design of a pivotal study towards the end of next year. Now the way we think about the expansion of the obe-cel opportunity, there's sort of 2 directions or 3 directions we're going. One I just talked about, which is taking obe-cel into additional indications, the one have on Hodgkin's space that I'll talk about briefly, but they're also obviously the [indiscernible] space. In addition, we look at AUTO1/22, which was results from pediatric patients published in [indiscernible] about 2 months ago, which showed that we had a highly active product that also allowed us to be active in patients that were ineligible for KYMRIAH, which is the standard of care in that setting, including patients that have lost CD19 antigen. This program clearly is sort of a life cycle management program when you think of it to obe-cel on the oncology side because it addresses obviously, one of the rights of escape that we see with obe-cel, which is CD19 loss. Now the second program, AUTO8 is one that we'll talk a bit about in a minute, which is targeting CD19 and BCMA. And that's obviously primarily initially designed for multiple myeloma. And the premise behind the program is to address, on the one hand, on the BCMA side, have a product that can recognize cells that have very low expression of target antigen and on the CD19 side actually provide an ability for persistence and sustained activity over time. And if you think back of what we just talked -- what I just talked about with SLE, there's always been a hypothesis in multiple myeloma that the driving cell of multiple myeloma is an early plasma cell, which is likely CD19 positive. So that's on the upside of the equation. That's been very hard to prove so far. It's been a hypothesis for 30 years. It's been [indiscernible] ambiguous in terms of the data, but I think we have to keep testing. But of course, there's also a possibility when you think about autoimmunity that you have actually a disease that may be driven off plasma cells that are mature plasma cells. At this point, everything that was looked at in [indiscernible] and in all the indications would suggest it's CD90-positive population of plasma cells that actually are the culprits. But we do not know the effects8 for many of the autoimmune indications, that's one of the areas we need to explore. But clearly, AUTO8 gives us an ability and a product design that allows us to go there, should that become necessary. Here is just a quick look in terms of our experience also from the ALLCAR extension that Claire introduced before with patients with non-Hodgkin's lymphoma and CLL. What we do have is very high overall response rates, you see CRs in the majority of these patients. And what we do see is also very nice persistence in many of these patients, which is shown below the table. And when you look at the right-hand side, you can see the [ swim ] plots, and you can see that we have many patients out for quite extensive period of time. What's very encouraging overall, obviously, the experience in [indiscernible] cell, but also CLL starts to look very interesting in terms of the activity and the sustained nature of the activity. Important here, again, the safety profile is exceptional in these patients. They receive a single dose. And when you look at the profile, clearly, will be supportive of our patient use in any one of these indications. Now a quick word on AUTO8. So I mentioned the fact that this is a product that has 2 chimeric antigen receptors, one is for BCMA, the other one obviously being the CAR for obe-cel. And on the right-hand side, you basically see some of the characteristics and there was more details shown yesterday on how we actually went about designing the BCMA portion. And importantly, what you do see is that the binder and the CAR that we were going for on the right-hand side actually had much more potency against low expressing target cells than any other product either from our side, whether it's bb2121, which is the equivalent [indiscernible] or [indiscernible] which is equivalent to [indiscernible]. So it is a much more potent CAR that we designed. And you saw for those of you that say in the room, you saw it was both about the binder as well as the actual architecture of the CAR which is different. We then actually took this in a study, which is the McCarty study that has 2 cohorts. We wanted to have first actually establish the activity of the BCMA CAR alone so that we would know actually when the CAR does what it was supposed to. And as we start to have information on that, then add the second CAR kit, obe-cel basically to it, and with that thing to look at, do we have an impact on cellular kinetics in particular, in these patients and whether we have seen any other impact, particularly longer term, which obviously is something we're still in the process of observing. The initial data is very encouraging. All patients responded to therapy. Most of them have already achieved a CR. And typically in this space is that you go from a PR eventually to a CR because you look at clearance of paraprotein and depending on the nature of paraprotein can be very long list. And so you need to actually -- this actually has usually a progression, but you see a remarkable level of activity where the BCMA CAR was used alone or in combination with obe-cel. The safety profile was very encouraging. We had no ICANS whatsoever in these patients, and we had no high-grade CRS, either in these patients, although we had very high levels of clinical activity. One thing that was also shown yesterday was actually cellular dynamics. And one of the interesting we start to see is that when you add obe-cel component, the CD19 component to the product that actually the persistence starts to build. And there was some nice fact [indiscernible] shown by Lydia Lee, who presented -- did the work and presented it yesterday that actually really nicely illustrated in fact that indeed, you start to see very nice enhanced persistence by adding the CD19 component. Obviously, this is early days, more data to be generated, but a program we're excited about. So with that, obviously, there's been a lot of news flow that we had, particularly towards the end of this year. We expect to start our quite advanced engineered program in neuroblastoma or 6 NG. The study is open. We're enrolling patients on this program. This is a program that you may remember, has 5 cell programming elements in it and a program very excited about to see what the technology have developed in the last few years can actually achieve. The study on that one is called [indiscernible]. And then obviously, the SLE study starting early next year. And then I think in terms of the regulatory steps, the next key step will be the validation period through, which is a 60-day time point after filing where you know actually where the filing is accepted, and you will also -- we will know at that point in time whether we get priority review or not, which, frankly, at this point, is difficult to predict. So with that, I think we're going to get close to the Q&A session. Just to remind you, obviously, we're in a growth spot. We believe with obe-cel, we're on track moving forward towards the regulatory review process. And we are executing on the pipeline as well, as you've seen with a number of data sets that we shared with you. Overall, we're in a good position from a cash perspective, have an adequate runway with the business that allows us to get 3 of the key regulatory steps and then obviously drive the program forward and the company forward from there. So with that, I think we're going to move to Q&A.

Yanan?

Yanan Zhu, Wells Fargo. I was wondering about the response rate and EFS from the [indiscernible] cohort, i.e., what might appear in the product label. How would that look compared to the [indiscernible] analysis? And when might we see that data? That's the first question. And the question regarding to your comment about persisting CAR T in the SLE -- in that kind of setting. We saw the B cells begin to come back after 3 months. So I was wondering how does that sit with the kind of hypothesis of persisting CAR in that setting?

Very good questions. And so the first one is in terms of the activity for the patients with morphological disease, which are the patients that actually will go into a label. As you've seen in the data presentation that the ORR for these patients is 74%. So that is very similar, although we have slightly more patients in this analysis and the 76% that we have reported at ASCO, where we had the smaller -- some of smaller data group. It is -- that's unchanged, and that's going to be -- that's the range of ORR that we have with the product. In terms of the time-dependent outcomes, we expect those to be at the time of the label similar probably to Tecartus and that is mostly an impact of the time of follow-up that we have with the program at the time of filing. What we did see and this is the important part of what we presented today is that when you look at the overall population, you look at the intent-to-treat population where we're clearly going to have a superior profile because we have more patients treated and we had overall, obviously, a very nice outcome as you've seen today. What the physicians are looking at, and this is very interesting is obviously, what they are presented. The physicians are going to look at the totality of the data. And they're also going to look at the impact of the patients that were intended to be treated. Because that's when you make the treatment decisions. Screening, that's really make a deeper treatment decision. And from there on, the [indiscernible] therapy. That's also -- and that's actually the key way on actually how the physicians are looking at it. And that's interesting because there is a discrepancy there to some extent between the rate at where regulatory review will look at it and the way that the treating physician will look at the data. And it's also actually a difference in terms of the agencies. The agencies are not actually homogeneous in the way they look at data. You have -- the FDA looks very much at the patients in terms of the disease burden at lymphodepletion. We'll look at that. That's the primary observation. The European agency will have predominantly have intent to treat because they're looking at what's the decision that the physician is making and what is the outcome that it can generate. So even there, the regulatory authorities actually take different physicians of what they think matters. But they run the analysis in slightly different ways. But overall, we are going to be in a very nice spot. The safety profile is remarkable. And the efficacy profile in terms of the key parameters will be similar. And certainly, from a statistical perspective given the size of the studies we have no way to disseminate these outcomes on these point estimates. Yanan?

On the SLE...

On the SLE question on the persistence. And I also appreciate you asking the question because I [indiscernible] for that question, I guess. But it's interesting when you look at the product, obviously, that was used in [indiscernible], as indicated in pediatric patients late to 2 to 3 years and maybe even the times longer persistence in these patients. Very, very similar to what we're seeing with obe-cel. Now that persistence is substantially shorter in patients with SLE. The primary reason is that SLE patients or [indiscernible] patients have a normal immune system. They have an [indiscernible] that's out reactive. But other than that, the immune system is [indiscernible] a normal immune system. It's not immune suppressed as an ALL patient actually is. And as a consequence, you do see substantially shorter persistence in these patients. But it doesn't mean that short persistence is what is needed. It's a lung persistent CAR but in those circumstances last for that period of time, and that drives the outcome we've seen. We don't know if you could generate these outcomes for [indiscernible] That's kind of -- I was raising the point because that was one of the things that I think that misunderstood in the communication [indiscernible]. Mara?

So I wanted to ask a question, maybe this is appropriate for Dr. Roddie, but you alluded to the different approaches that the regulatory agencies take as it in terms of looking at different the patient populations [indiscernible] clinical trial. And so I'm curious from Dr. Roddie's perspective, how readily that will be incorporated into practice even if the only data that's on the label is the morphological group data, but you've got these other cohorts published. And then secondarily, maybe if we could also talk a little bit about understanding sort of sequencing of obe-cel relative to blinatumomab for patients from a practical perspective?

Yes. Very good. I'll start there and then I'll hand off. I think what's very interesting is in this field is that the treating physicians are a very small group of physicians. We're talking, as I mentioned before, somewhere in the range of 60 centers treating at least 90% of the patients in the U.S. In those 60 centers, you may have somewhere in the range of key physicians, 3 or 4 physicians treating these patients. So it's a very small group of physicians. And all of these physicians are very similar to Claire, physician scientists. And that is very different from many other settings, which is that, that group is driven by actual clinical data. And much less by what the label will state because they look at the data, they evaluate the data, the interpreted data as well. Is this a real-world situation? Is it not? Does it reflect what my patients look like or not? And that's why this is a very different space where, in fact, with the published data, the actual clinical data has a different rate, but Claire, please chime in on how you actually make decisions and how you inform yourself?

Just in -- I mean, the label will be really important because I mean, I can only speak to the U.K. experience where the access to CAR T is driven by a sort of a centralized panel through NHS England. So it's all sort of overseen and from the NHS England. And so they have a stipulation for what criteria patient [indiscernible] meet in order to qualify for eligibility. And if the label says you have to have 5% for more blast then that will be the criteria that we'll need to meet in order to get that patient access to the product at the point of screening. But again, if the patient gets a good response to bridging, for instance, when they end up with an MRD negative response to bridging that will not preclude administration of that product. I think we'll struggle to get extramedullary disease in at the point of screening unless it emerges sort of post screening, and we treat it as part of the sort of a larger ALL piece. And I guess it will have to be to Christian and the team at Autolus to see whether or not these indications can be expanded on the label at some point in the future. And the second question was about [indiscernible] blended [indiscernible], wasn't it? I mean I think the reality with blinatumomab visit, and particularly in the U.S., everybody seems to be pushing towards using it upfront as possible. And if you listen to [indiscernible], that's all we'll talk about this using [indiscernible] and [indiscernible], et cetera, et cetera. So I don't think we can ignore the fact that that's the direction of travel for a lot of ALL. But I think the data that we have on the prior exposure to blinatumomab you might remember the forest plot, and there was a sort of an inkling that perhaps prior exposure to blinatumomab potentially pushed you a little bit towards the ORR. But actually, when you separate that data out and you categorize it according to [indiscernible] followed by allograft versus [indiscernible] nonresponder refractory. It's a totally different picture. Because it's the refractory patients, who are the ones who are doing worse and that might be giving us a feel potentially for those are patients with perhaps some sort of [indiscernible] or some. Maybe it's a heavy pretreatment or whatever. But it's not across the board. The blinatumomab is bad news for CAR-T. It just is in sort of refractory patients that skewing that result. So I don't think the blinatumomab is going to sort of change the paradigm. We're going to impact upon the value of obe-cel. I think it will be a population of patients I think if you ask [indiscernible] to borrow the same question he would say the same thing. There are patients that we know who are likely to be refractory to all sorts of chemotherapies, people with TP53 mutations, people with MLL, people with complex carrier type [indiscernible]. Those are populations who we know [indiscernible] allografts won't be particularly effective in allogeneic stem cell transplant in ALL, it's really predominantly -- it has its impact through the high-dose chemotherapy rather than the sort of [indiscernible] versus leukemia effect. So these are patient populations for whom the point [indiscernible] here, we would love to see a study where we could take those patients upfront and put those patients into a party for the future. I think that's a sort of a population that would benefit. But on the board terms of sequencing, I don't think we can get away from blinatumomab, and I think I would urge you to consider that blinatumomab does not mean the CAR T-cell will not work for this patient population.

And Christian, if I could just ask on the fees. One lupus trial, the SLE trial. Will you be collecting data -- disease modifying data on to organ fibrosis, we'd be looking at that?

I mean that type of data actually gets typically reporting or also falls into the composite scores as well. So you have that quite totality of symptoms changes in organ function as well as if you look at proteinuria as well as obviously fibrosis, which you can look at by imaging, to the performance on other reactive antibodies, so the disappearing sort of change in the level of double-stranded DNA antibodies and so on for all of that, this part of the standard panel that you would look at in these patients. And maybe one to add on to Claire's point about the sequencing. What has been very interesting to see in the ad boards that we're running, is that there clearly is a view that there is an interest in actually moving OB ahead of plan in the relapsed refractory setting. Obviously, as [indiscernible] goes up in the front line, and the patients are relapsing interest is to move OB up, particularly if there is a belief that indeed you can actually generate a long-term outcome as a stand-alone therapy because everything else you do will require some form of consolidation as well. And that change in sequencing in the relapsed-refractory setting was interesting to see pop up very early on in these interactions, and we expect that is certainly a feature and a theme that we're going to be seeing as well.

Kelly Shi from Jefferies. So on one of the Slides, it was no data, 15% of the patients on [indiscernible] were admitted to ICU. Curious on could share more information on -- trigger this ICU space. And also curious, what is the ICU admission rate across other CD19 CAR product adult ALL0 and in the broader [indiscernible] indications? And what are those numbers [indiscernible] on SLE?

Yes. Very good question. I'll start and then hand over to Claire. Obviously, the reason for why patients go in ICU is actually manyfold. One of the issues that you have with many of these patients that they can actually develop infection and sepsis. And that often is a reason why you may actually have to put them in ICU. So there's a series of events that are disease-related and there's a series that could be related to the therapy itself. And I'll talk about it. One of the parameters you may have seen is only 2.4% of the patients on vasopressors, which use as an indicator for why you would actually have to move a patient to an ICU because of the CLS, okay? So that already [indiscernible].

Yes. I mean there was the ICU, the admissions for immunotoxicity that was about 1/3 of the cases was directly for the management of immunotoxicity. There was one patient who was transferred to ICU for more in-depth monitoring, so they needed more intensive low pressure partway monitoring, et cetera. So that was 1 additional reason. And as Christian says, infection. And actually, if you look across the board, [indiscernible] patients who are receiving non-CAR T therapies in the context of heavily pretreated ALL. This is not surprising a finding. We see a lot of patients with quite significant infections because remember, they both have conditioning chemotherapy and they're all neutropenic by this point also. And so you can see this across ALL. And then I think it compares favorably with what's been described in other studies, and certainly in the ZUMA-3 study, they were a higher proportion of patients require intensive support and there are certainly more patients that required vasopressors. So I think it speaks to the kind of toxicity profile that we've talked about quite extensively in this meeting and this is a much better tolerated considering we're treating these a lot of older patients as well. And or the patients with the [indiscernible] disease, and we're definitely moving in the right direction with this product.

So clearly, on the vasopressor side, the core [indiscernible] was 40% on vasopressors, not 2.4%. And obviously, about 5% on [indiscernible] study that would be related to [indiscernible].

And also for the AUTO8 CD19 BCMA dual CAR, you have showcased the first promising data yesterday in [indiscernible] regarding the CAR design, you mentioned you have a sensitive BCMA bender. So do you have a concern for this increased bending to arterial tissues such as CMS due to a sensitive [indiscernible] for underlying indications because the higher [indiscernible] safety? Or should I think any like a synergy between this sensitivity [indiscernible] CD19?

So a few things out there. So one of the things was the concern around that you might actually induce neurological toxicity with these types of products. And I think part of that is that we've seen for one class of BCMA CAR, we see in Parkinsonism, with the other kind of BCMA CAR, there's no such data available. It doesn't seem to be happening. I haven't heard any data coming through the third developed product that is very far along or moving along. So it's not clear that this is a product-specific issue that was described for the 1 product or not. We haven't -- we would think that based on the experience that's there with BCMA bio specifics as well who also can actually get into the [indiscernible]. But it doesn't look like there is a general BCMA risk for that type of adverse event. But we'll have to see as more data is generated. In our own hands, as you've seen before, we haven't seen any ICANS whatsoever. And I think that is sort of probably where we need to go by at this point in time. If this is the profile that we can see sustained, then I think it's a very attractive growth plan. Asthika?

Next question, Asthika Goonewardene from Truist. I got a multi-part question on transplant to [indiscernible]. So [indiscernible] decision to put a patient on transplant? And second, in that below 5% to [indiscernible] groups, could you estimate the frequency of proportional portion of non transplant? And also in these groups, did you and colleagues feel comfortable and making a decision to spare patients from going on to transplant?

Yes, it's a multipronged question. So in terms of [indiscernible] transplants, it was 17% of the patients overall received transplant. And I don't have the [indiscernible] line in front of me as to the what sort of groups that they fell into in particular. It wasn't my decision to push them towards transplant. It was very much an investigator-driven decision, and there's a sort of there's a strong view with some investigators that a CAR T-cell should be consolidated. So I think it's quite hard to dissuade people from doing that. So these were decisions that were driven by the sort of local investigators. The majority of the transients that were given on this study were first transplant, but 5 of the patients received a second transplant. And I think that those patients did particularly badly. I think there is no room for second transplant in this space whatsoever, and I actively discourage colleagues from that practice across the board. When we look at the outcomes per allograft compared with patients who didn't go on and have an allograft, actually, it's an interesting finding. You find that the sort of the EFS is slightly lower for those patients who had a transplant. So there's certainly -- there's an indication from this data that transplant is not enhancing these patients' outcome. There's no substantial benefit to begin from doing so. And from my understanding it's not that there were some accruals to bide and between the patients who are tend to have a transplant versus not in terms of the demographics. So that's the information I have from the statistician on the study. In terms of what drove the decision to go to transplant, it's not that the patients lost persistence because actually the majority of patients who went on to receive a transplant actually have ongoing CAR T-cell resistance. And as we are all familiar with in the rim, transplant has not only a high treatment-related mortality but also there's an incidence of relapse. Then in fact, if you take a patient, who's got ongoing CAR-T cell persistence with B-cell they were ongoing B-cell [indiscernible] representing sort of like a functional engraftment of their CAR and then you give them a transplant and you obliterate that far, really, you're putting that patient at pretty high risk, potentially overlaps and particularly in those patients book, as I say, the high risk, the TP53, the MLL, the complex [indiscernible], et cetera, those are patients who we know that won't benefit from the transplant anyway. So I think we have to sort of -- there's a bit of a paradigm shift here in terms of the rule of allogeneic tstem cell transplant [indiscernible] I think we can acknowledge that certainly over 75% bone marrow blasts bracket is a tricky one to contend with. And I think as a stand-alone therapy, that's a much more contentious point. And maybe you would have to counsel patients in that bracket for consolidated stem cell transplant should be considered, but certainly not a second transplant. The first transplant, I think will be the recommendation for treatment -- for transplant naive patients.

And Christian [indiscernible], just as a quick question on AUTO8. Can you talk to us a little bit about your plans to commercialize this product going forward, given that there's a competitive space. Do you feel we need to have a partner for this? And maybe what your long-term strategic thoughts on that?

Right? So when we look at the multi myeloma space, we believe, actually makes a lot of sense to consider a partnership. And this is, to your point, very competitive, but it also requires very substantial investment because it will basically run a late line or late-stage study give it a first line study. But in parallel, we'll have to [indiscernible] on a second or third line study just to be able to actually move sufficiently swiftly through the development cycle and position your product. So that's certainly one of the areas we're looking into, and I think this will be attractive for us to consider that. Gil?

Gil Blum from Needham & Company. My question is kind of on the bridging aspect. [indiscernible], we saw that graph that show that on average, the type of bridging didn't really change that patient outcome when it comes to blasts. As a clinician, we get a patient with very high 75% blasts down. What is your thinking about how you're going to bridge that patient to get a better outcome?

I know. I mean there's no part of the [indiscernible] there. It's actually -- and if you look across the different centers, the practice varies wildly between different clinicians. On the whole here, 80% of patients received a chemotherapy-based bridge, plus or minus TKI, in some cases, plus or minus, initizumab and others. And my sort of like rule of thumb is that the patients have got a significant disease burden and they're positive for CD22. And I don't -- it doesn't need to be strongly positive. You can have 5% or more. So it's quite low -- it's sort of a little bar, but I would be [indiscernible] setting and I might curtail the dosing. So I might give on one out of the 3 doses that would be recommended standard practice with the objective of reducing down that stuff burden with the immunotoxicity and potentially from the EFS perspective. For patients with lower [indiscernible] garden disease, who patient presents maybe sort of less than 10% blasts, for instance, or even sort of at the level of 5% blasts that would probably use in context because it's well tolerated, it'd be quite easy to administer a patient therapy. So that's the kind of the hard and fast sort of rules that we use in our own roaming center to try and manage the risk.

And given the results from the MRD-positive cohort and also what you've seen in transplant it kind of suggests that maybe there's a path forward here as a -- let's call it, the transplant advisement. You can get the patients in [indiscernible] positivity, which given obe-cel.

That's a trial that needs to be done with, isn't it? Looking nowhere in particular.

I'm just looking for the check book. It's an important question. It's no doubt about it. It's a key question to us. James?

James Shin from Deutsche Bank. Sort of big question here. What was the EFS for the Phase Ib portion of FELIX. Assuming the 20 ALLCAR19 patients had an EFS of 20 months, I think that was presented at ASH 2021. It seems FELIX's Phase Ib EFS was little bit lower, buyback with the envelope map points around 6 months to arrive at full to 9 months, I see today. FELIX Phase Ib EFS indeed lower? And was this lower EFS attributed to COVID. That's question one, sorry for the length of it. And then along that side, what was the EFS for the Phase II portion of FELIX. It seems like the Phase II portion of -- Phase II [indiscernible] 12.5 months, which is more in line with the Phase Ib that we saw in all finance.

So it's -- I'm always amazed with the amount of reengineered data that you guys are going through. So first of all, hats off for doing the work. The -- I think you're actually, I think, from a trend perspective, I think you're looking at this the right way. The Phase Ib portion of the FELIX study was a little bit below where all ALLCAR19 came in. And we believe that actually had a lot to do with the challenges that we went through. I mean this is 2021 where we don't start it during that period, just to give you a feel UCL shut down as one of our key centers and pretty much every center in the U.S. eventually shut down. So it was a very, very challenging period to go through. So the patients were in extremely poor condition, particularly during that phase and into the early part of 2022. And I think that actually clearly contributed to that slight difference. It wasn't a big difference, it's slightly reduced. And I think the trend that you sort of indicated, I think, is about right with regards to the Phase II portion. Matt?

Matt Phipps, William Blair. I'll ask one on SLE. How are you thinking about the criteria for your initial enrollment, your inclusion/exclusion criteria as far as maybe patient age or time since diagnosis or [indiscernible] baseline. And then when do you think you'll disclose any additional autoimmune indications? How are you thinking about those beyond SLE?

Right. So think of the trial that we're planning to run as looking very, very similar to what Andreas and [indiscernible]. The same type of patients that we're looking to enroll, a lighter patient age range that we would allow, but they tend to actually cluster more in that earlier teenage to mid-20s and 20s range. So that's just a question of distribution of when you look at the severe or refractory patient role in particular. So it looks very, very similar to the way that we actually designed the study. What we're doing differently in the study is that we're using a fixed dose. Obviously, our product obe-cel in pediatric patients is also dosed -- there's 1 million cells per kilogram. We have a huge range of age in on the pediatric side and also the currently ongoing study that we're running the youngest child that we had we started looking at was a one year old and you can have -- but then you can have a 16-year-old at 100 kilograms. I mean you can have this wide range, which is why you have this type of a dosing. That, of course, doesn't make sense when you actually deal with adults. And so we're going to use a fixed dose in this setting of approximately 50 million cells total dose. And that also is very practically driven because it gives us a good volume. So it's easy to work with. If you're going to smaller doses, actually the volumes get small and it's actually more difficult to handle. And it also gives us, I think, plenty of activity. You've seen Claire talk about patients who have received 10 million cell dose with this astronomical levels of [indiscernible] that got into complete remission. So we know the product is hugely active and we're for very practical reasons are picking a dose level that is easy to manage and easy to handle in a real life setting. And then the second part of the question is when we will consider to move beyond the initial step we're taking. So step one is actually determining and establishing, confirming that dose, that's step one. Once we've established that, that's when we actually are considering to branch out, along the direction goes to pivotal study in SLE and/or [indiscernible]. And on the other hand, we're considering running a basket study to explore the activity of the product across the range of autoimmune indications. We're still pretty small in terms of data sets across many of these indications. I want to understand what the profile of the product is before we would make decisions into additional indications beyond the 2 or 3 that are very clear at this point. All right. So I think with that, first of all, I'd like to thank you all for coming. We slightly went over time. I'd like to thank Claire for a fantastic job and for your time and sharing your insights with us. And really looking forward to keep you updated and continue the conversation. Thank you very much.