I would now like to turn the conference over to your host, Olivia Manser. Please go ahead. Thanks, Andrew. Good morning, all. Good afternoon, everyone. Thanks for joining us on a Saturday to discuss our data from the pivotal FELIX study of obe-cel, which was presented yesterday at the ASCO conference. With me today are Dr. Christian Itin, our Chief Executive Officer, and we're really grateful to have Professor Claire Roddie, Associate Professor of Hematology and Honorary Consultant Hematologist, Cancer Institute, UCL, University College London, on the call today to walk through the data that we presented yesterday. On slide two, before we begin, as usual, I just want to remind you that during today's call, we will make statements related to our business that are forward-looking under federal securities laws and the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These may include, but are not limited to, statements regarding the status of clinical trials and development and/or regulatory timelines for our product candidates. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward-looking statements and for a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's or yesterday's press release and our SEC filings, both available on the investor section of our website. So on slide three, you'll see the agenda for today's call. Christian's gonna set the scene on obe-cel and the FELIX study results to date, and Dr. Roddie will then run through the slides that were presented yesterday in an oral presentation at ASCO, and Christian will then close the call before we take Q&A. Over to you, Christian. All right. Well, thank you very much, Olivia, and welcome everybody to our call this morning from ASCO. Pleasure to have you all on, and also a pleasure to have Claire actually walk us through the data that were presented yesterday. On slide four, just as a quick overview where we are with the company and where we stand with the program overall. As you remember, we did our first presentation of the FELIX data, the first data cut that we had of the full study, a year ago at ASCO, here in Chicago as well. And we're now obviously at a point where we have substantially more follow-up data, and that's gonna be really the key part of the topic for today. Start to develop a very good understanding of some of the... and some of those aspects will be highlighted today in Claire's talk. Just as a background, you may remember that we have filed for an approval in the U.S. as well as in Europe. The PDUFA target date in the U.S. is November 16 this year, and that's obviously an ongoing process and review process that we're in the midst of and just a bit over halfway in that review process. We're pushing obviously the program further into additional indications, and there's gonna be more updates towards the end of the year within that regard. We also have announced, obviously, that we have received a license from the U.K. agency, the MHRA, for the production of obe-cel at our new manufacturing facility, The Nucleus, in Stevenage in the U.K. We are obviously now in the process of preparing for launch and make sure we're ready by the time we get through the approval. Finally, obviously, we have also announced earlier this year a set of transactions, obviously, important transaction for us with BioNTech, as well as a capital markets transaction, which puts it in addition and gives us a strong foundation to be in a position to launch the product once we achieve and receive the approval. So what I'd like to do, going on to slide number five, is just briefly look at a few aspects of the data that we have presented at the end of last year. These are areas that obviously are key aspects of properties of the product that we're not gonna be actually repeating on in today's presentation, but obviously are important to sort of keep in mind. Going on to slide number 6, just to kind of remind ourselves actually, when this study was actually conducted, when the patients were enrolled and were being treated. In fact, as you remember, we did actually start enrolling into the phase I portion as of June 2020, and then actually finished the phase II portion enrollment at the end of November 2022. So we're kind of in the height and through the height of the pandemic, and you can see on this chart in the blue charted area, we see the various peaks that we had seen on infections, that we all have a collective memory on how that was. But also what I think is important, it gives us a sense of how massive the impact actually was, on a lot of aspects. In this case, one of the parameters we look is obviously the national flights from the U.S., and you can see in the green line that there was huge fluctuations in the availability of flights, between the U.S. and obviously, in this case, our manufacturing site in the U.K., from which we supplied. Now, despite all this fluctuation, all these challenges and logistics, etc., we're able to actually have very steady supply of the product with very consistent day to delivery times throughout the entirety of the trial. You see this little fever chart in the middle, there you see literally every individual product plotted over time and the actual length delivery time that the product actually had over that period. So we were able, despite all of this very volatile background, to actually deliver very steady, very consistent product throughout the entirety of the study. And that's obviously an important aspect as we prepare for commercialization, is that a lot of the systems that we built, the delivery, product delivery capability, the logistics, etc., have been pressure tested to an enormous extent during the contract.... I think the other aspect, I think I just want to highlight here is, obviously, one of the things that we were certainly very mindful about as we're conducting this study during this period, was that we had to actually be aware that there was a lot of things that could happen during that period. We had, you know, many of the hospitals shut down at one point or another. We're not able to recruit patients, were overwhelmed with too many infections. Their ICUs were overwhelmed, et cetera. So there's a lot of variability in there, and as a consequence, we also made sure that as we were setting up this study, that the physicians would have an ability to actually manage the patients in the best way possible and with as much flexibility as possible. And this is also why we didn't put in any constraints with regards to their ability to bridge patients, and also included agents that are very active agents like inotuzumab, and allowed those for the bridging therapy. This is important because obviously it has, it creates, a backdrop within the study, which is a very real-world type of backdrop. I think it's also what resonates very well as we're sort of presenting the data now in various venues. I'd just like to highlight three items and three features of the program, and then we're going into the update that Claire will present. Going on to slide number seven, one of the hallmarks that we started to build, and we started to get actually see develop over time, is that it looked like we're starting to see a stabilization of event-free survival in the patient in the patients that were treated on the FELIX study. Which would be indicative that indeed, there is a proportion of patients that have a chance for long-term outcome. This is a curve that's reminiscent and in fact, was superimposable to the curve that we had seen in the old CAR-19 study, the phase one experience that we had that led into this pivotal program. Now, obviously, there were still, as we were at ASH, end of last year, there's still a limited number of patients who are in the outer part of the curve, and also getting more follow-up will give us much more confidence around the ability to really predict longer-term outcome, in this, in the study. Now, when we look more closely on the next slide, and we're asking the question: Well, what is the impact of tumor burden and lymphodepletion on the outcome? What you can see is the patients had, in the blue curve, a very tumor burden below 5%, that those patients had a remarkable, chance for long-term outcome, and you see that the EFS stabilizes at around 70%. Patients that were sort of in the intermediate range between 5%-75% of tumor burden and lymphodepletion are the green curve, and you can see they're still hovering around 50%, maybe slightly above it. It's only the patients that have very extreme levels of tumor burden of 75% after bridging therapy and are basically, you know, refractory to bridging therapy. Well, what you can see with those patients is that they still have an overall remarkably positive outcome when you look at event-free survival, but clearly running below the patients that had lower levels of tumor burden. So give us a good indication of the impact of tumor burden and lymphodepletion on ultimate outcome with these patients. The other aspect, which is clearly a hallmark on slide nine, of the FELIX, of obe-cel, and what we were observing both in the old CAR study but also in the FELIX study now, is that the product has a remarkable safety profile. Here we're looking at immunological, toxicities, and we looked at cytokine release syndrome and neurological toxicities reported as ICANS. And what you can see is that overall, the high-grade levels, which are the dark colors on the left-hand side, are very low. We had 2% of patients experience high-grade CRS. We had 7% experience high-grade ICANS. This is actually a level of immunological toxicity that is numerically below of what was reported for Blincyto. So this is quite remarkable. Now, when we then look at the, how these events actually were distributed across the level of tumor burden and lymphodepletion, what you can see is that but with increasing levels of tumor burden, you'd see also an increased level of immunological adverse events. But overall, it is still low. So even patients that have more than 75% tumor burden, had in the range of 3%-4% high-grade Cytokine Release Syndrome. So still very limited and very different from the experience that the field had with other CAR T programs. When we look on ICANS, again, very limited levels, and in fact, when you look overall at the numbers for above 75%, those actually are still at, very much in line with not the high dose and not the high tumor burden experience, but the overall experience that physicians have with Blincyto. So it is a remarkable profile and also indicates that patients that have very low tumor burden, below 5%, have a remarkable safety profile and combine that, obviously, with a remarkable event-free survival that we have seen on the slide before. So these are some of the hallmarks that we have seen. Those are part of the analysis that we have shared at the end of last year. So the focus of this presentation is somewhat different. It looks more into the longer-term outcome, but it also starts to look at the impact that we would see with additional therapies that the patients may experience. So with that, I'd like to actually hand over to Claire and move to slide number 10. Great. Thanks, Christian. Can you hear me okay? All good. Okay, excellent. So thanks very much for inviting me to share the data. So it's great to see it mature the way it has been. If we move on to slide 11, that's our title slide for the presentation that Elias delivered yesterday. So essentially what we're talking about in this presentation is it's the obviously obe-cel in the context of adults with relapsed and refractory B-cell acute lymphoblastic leukemia, which obviously we've spoken about in previous occasions. And here we're looking at the persistence and really the impact of consolidated stem cell transplantation in the context of our FELIX study. So if we can move on to slide 12, please. Essentially, this is a really helpful slide because it's just, it's giving you sort of like a précis of what we really feel are the main takeaway messages here. I suppose the first most important thing to say is that, after obe-cel infusion, and this is at a median follow-up of 21.5 months now, that 40% of responders were in ongoing remission, and that's without subsequent allogeneic transplant or other therapies. It's important to note that both the event-free survival and the overall survival outcomes show the potential for a long-term plateau, which is, of course, something that, you know, was very exciting about the ELIANA study in pediatrics. And so we're really sort of heartened to see this as sort of a similar, plateau emerging in the adult ALL setting. And today, really the focus is on presenting data, showing that transplant consolidation for patients in remission following obe-cel, it doesn't seem to confer better survival outcomes, but we'll go into that in subsequent slides. Additionally, a really important take-home message here is that ongoing CAR T cell persistence was associated with improved event-free survival in this analysis. So if we move on, we're on to slide 13 now, and a lot of the callers will be familiar with this background, but essentially, obe-cel, as we know, is a unique CD19 targeting autologous CAR T therapy, and with this fast-off rate, CD19 binding domain. It was really sort of designed to improve CAR T persistence and reduce the immune-mediated toxicity Christian was mentioning before. It's under investigation. As we know, in adults with relapsed and refractory acute lymphoblastic leukemia in the context of this FELIX study, and the FELIX study has been an open-label, multicenter, single-arm, Phase 1b/2 study. Now, the safety profile of obe-cel, also evaluated in FELIX, has previously been presented in detail, and it won't particularly be discussed during this presentation. Instead, today, I'll really be focusing on event-free survival, overall survival, and really the impact of CAR T persistence on stem cell transplant, in these patients treated with obe-cel. And so if we move on to slide 14, this is really our study design slide, and it's just showing us the sort of tumor burden guided split dosing that we previously discussed. The split dosing, as we know, it's based on the pre-lymphodepletion tumor burden, such that on day one, patients with 20% or less bone marrow blasts, i.e., low tumor burden, and were able to receive a higher initial dose of CAR T cells. That's 100 million cells, while those with over 20% blasts or high tumor burden received a lower initial dose of 10 million CAR T cells. But at day 10, if the CRS was grade one or lower, and ICANS was completely resolved, the second dose, i.e., dose two, of obe-cel could be administered in that setting. And then in the low tumor burden category, those patients would receive 310 million CAR T cells, pardon me, while those in the high tumor burden category received 400 million CAR T cells, to a total of 410 million CAR T. And if we move on to slide 15 now. This slide is really just summarizing the patient eligibility and endpoints. And across the Phase 1b and the 2 of the FELIX study, obe-cel was administered to a total of 127 adult patients, and the patients were enrolled into three main cohorts, and that depended on their disease characteristics at screening. So Cohort A comprised patients who had at least 5% bone marrow blasts or morphologic disease. Cohort B comprised patients who were MRD positive, and that they had greater than 10 to the - 3 leukemic cells by NGS testing, but fewer than 5% bone marrow blasts by morphology or flow. Cohort C comprised patients with isolated extramedullary disease. Now, the primary endpoint was the rate of CR and CRi, and that was conducted by independent review. Secondary endpoints included duration of remission, EFS, overall survival, and MRD negativity rate, and that's defined as less than 10 to the - 4 leukemic cells. Of course, we were also focused on, in the secondary endpoint, on safety, CAR T persistence and manufacturing feasibility. If we move on to Slide 16. Here, we're actually looking at the patient baseline characteristics, and I think we can all agree, looking at this slide, that this is a heavily pretreated patient dataset. These are all the infused patients included in Cohort 2A. That's those patients with more than 5% bone marrow blasts. This was really used for the primary efficacy analysis of FELIX, and all 127 infused patients included across the Phase 1b and 2. Now, the median age was 47 years for all of the infused patients. As you can see here, and the median number of prior lines of therapy was two, and that varied from one up to as many as six lines of prior treatment. 42% of these patients had previously received blinatumomab, 31% had received inotuzumab, and 17% have received both. 44% of these patients have had a prior stem cell transplant, and at screening, the median bone marrow blast percentage was 40%, while extramedullary disease was reported in 23% of our patients here. Now, if we move on to Slide 17. Here, what we're looking at is really the response rates observed across the study. So of the 127 patients who received the obe-cel infusion, that's 99 patients or 78%, achieved either a complete response or a CRi, and that was determined by independent review by the data cutoff of February the seventh of this year. And that was with a median follow-up after obe-cel infusion of 21.5 months.... Now, at the current follow-up, the majority of responders are showing durable response. Among the 99 responders, 40% were in ongoing remission, and that's without consolidated allo transplant or other therapies, while only 18% actually went on to have a consolidated transplant while in remission. If we move on to the next slide, that's slide 18. Now here, we're looking at event-free survival, and actually, for the main analysis, the main, the median EFS, and this is with censoring post-transplant, that was 11.9 months, with an estimated 12-month EFS rate of 49.5%. Now, if you press next, you should be able to see, the second, curve emerge. That's in green. When you look at this as the EFS without censoring for subsequent transplants, and it looks from the position of this green line on the curve here, that the consolidated transplant did not seem to improve EFS in patients post-obe-cel. Now, the median time to transplant was 101 days. This is after obe-cel infusion, and all 18 patients who went on to have a consolidated transplant while in remission were MRD negative prior to the allograft, and of whom 80% relapsed or died post-allo ASCT. Now, of note, there was no difference in patient characteristics between those who had not received a subsequent stem cell transplant. Now, the last point I'll make about this slide is that 56% of the 18 patients had ongoing CAR T persistence prior to the transplant, and 80% of the patients who had the ASCT relapsed or died after the transplant. It is important, I think, for everyone to be aware of the fact that, you know, the transplant conditioning therapy tends to eliminate CAR T cell persistence, and that's clearly an issue in terms of the ongoing immunosurveillance. So if we move on to slide 19 now. Here we're looking at overall survival, and again, it's really showing us that nice the potential here for a long-term plateau. Now, when you look at the OS, the median survival here without censoring for subsequent allo transplant is 15.6 months, with an estimated 12-month OS rate of 61%. And if we click next slide, we should be able to see the green curve emerging. And what this is showing us is the EFS, where there's very little difference when we're looking at overall survival with censoring or without censoring. So implying that consolidated transplant for patients post-obe-cel does not actually improve the overall survival. So the potential of long-term plateau is seen for both overall survival and EFS, and that's similar to the trends that we've observed already in the phase I ALLCAR19 study, which also investigated obe-cel in adults with relapsed and refractory acute lymphoblastic leukemia. Now, if we move on to slide 20, and here we're looking at CAR T-cell persistence and predicted relapse. Now, in order to understand the impact of loss of CAR T-cell persistence on EFS, we performed Cox regressions, and that was using loss of CAR T-cell persistence by digital droplet PCR as a time-dependent covariate. Now, a similar analysis was also conducted for B-cell recovery. What we found here was that ongoing CAR T persistence and B-cell aplasia were both associated with improved event-free survival. As indicated by this hazard ratio shown on the left panel, the risk of relapse or death would be 2.7x as high upon loss of CAR T persistence, compared with patients with ongoing CAR T persistence, and its impact was superior to B-cell aplasia. And similarly, as indicated by the hazard ratio shown on the right panel, the risk of relapse or death would be 1.7x as high once patients had B-cell recovery. Now, of note, the 95% confidence interval did not exclude 1, and it is a numerically smaller effect compared with loss of CAR T persistence. Now, if we move on to slide 21, we're looking here at the landmark analysis amongst patients in ongoing remission at six months, and this is without transplant or new therapies. And really what comes out of this slide, and what's most notable is that patients with ongoing CAR T-cell persistence are associated with improved EFS, compared with patients who lost CAR T persistence. In fact, the median EFS for patients with loss of CAR T persistence was 15.1 months, while the median was not yet reached for those with ongoing CAR T persistence. So clearly, emphasizing how important the persistence is to the ongoing event-free survival in this group. Now, next slide is slide 22, and here we're really concluding. So it's really to summarize what we've just looked at. So at the current median follow-up of 21.5 months, 40% of responders were in ongoing remission without subsequent stem cell transplant or other therapies. Now, in the primary analysis, 12-month EFS and overall survival rates were 49.5, 49.5% and 61.1% respectively. Now, these survival outcomes also show the potential for the long-term plateau, which of course is so very distinctive for this CAR. Stem cell transplant consolidation for patients in remission following obe-cel did not appear to improve EFS or overall survival. However, ongoing CAR T-cell persistence seems to be very important, and it is certainly associated with improved event-free survival. So really to conclude, obe-cel could be considered as a standard of care for adult relapse or refractory acute lymphoblastic leukemia. If we move on to slide 23, it's really just to acknowledge everybody who's been involved in the conduct of this enormous study. And in particular, it's the patients, families, friends, and caregivers, and of course all our colleagues, the study investigators and coordinators, and the healthcare staff at the study sites. Thank you very much for your attention, and looking forward to the discussion. Well, thanks a lot, Claire. That was a fantastic presentation. Let me just briefly look at the upcoming to slide 25. As I mentioned in the introduction, we're obviously in the midst of the regulatory review process, both in the U.S. and in Europe. The target PDUFA date is November sixteenth, at the end of the year. Obviously, a key set of activities leading up to that event. From a data release perspective, we do expect those to update further at the EHA meeting, which is just about coming up within a week's time. And also, we'll, in addition to the update you just followed, and we're going through with Claire, we'll be updating in the impact of bridging therapy, particularly the focus on the impact of inotuzumab during bridging therapy, as one of the additional data sets we'll be discussing at the EHA. As well as look more closely at persistence and the sensitivity of detecting persistence, and how that actually impacts the ability in the patients as well, which will be a second, a third part of the presentations that are planned for EHA. With regards to the regulatory process, in addition to the work that we do with the U.S. FDA, obviously, there is more activity with the European agency, EMA, that will be ongoing through the course of the year. We also are expecting to file an application with the U.K. authority, MHRA. And then finally, we obviously started also work in additional indications and are currently running a dose confirmation study, which we expect to have initial data from by the end of the year. With that, I would like to stop here and actually open up for the Q&A. Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. One moment, please. Our first question comes from the line of Gil Blum with Needham & Company. Good morning, good afternoon, everyone, and thanks for taking our questions. My first one is related to current practice. How common is transplant consolidation when giving CAR-Ts to adult ALL patients? Claire, do you want to take that? Well, I think, I mean, it is a really pertinent question, and it's one of the biggest... Sort of, it's one of the hot topics in ALL. The decision is very easy if someone's had a prior allo stem cell transplant, because in a sense, you know, second transplant is something that we tend to sort of shy away from. So a lot of the patients that come through our clinic will have had a prior stem cell transplant, and in that case, we don't tend to consider consolidation after CAR-T with a second transplant, because historically, the outcomes have been very poor from second transplants. For those patients who are transplant naive coming into CAR-T cell therapy, at the current time, essentially we counsel the patients who achieve remission after a CAR-T about the watch and wait approach, i.e., just continuing to follow up some of the markers that Christian just mentioned, such as B-cell aplasia, MRD, and also CAR-T persistency. So we weigh up that approach versus the, you know, the risks and benefits of progressing to consolidated stem cell transplant. It's very sort of physician dependent in terms of the approach taken. Our own practice at UCL tends to opt for a more watch and wait approach in patients, particularly those with ongoing CAR-T cell persistence, and those patients with functional sort of B-cell aplasia, and also those patients who've come in with lesser disease burden. In patients who've come in with higher disease burden, and in those patients who lose CAR-T cell persistence, then in those sort of situations, we would consider a consolidated allogeneic stem cell transplant. But there's certainly, you know, I don't think there's a sort of a uniformity and an agreed sort of paradigm that's followed across the, you know, across the field in adult ALL. I don't think, you know, people have agreed what is the optimal approach. But on the whole, we tend to use the kind of the published information, which is, you know, patients with ongoing B-cell aplasia and patients who come in with lower disease burden. We use that as a sort of like a marker for sort of, you know, a better outcome post-CAR-T, and so we tend to be more confident with a watch and wait approach in those particular patients. Christian, I don't know if you would add to that. Yeah, I think that probably what I would add is if you look at our field here, is that I think that the key experience is that the only way that we could actually see a chance for long-term outcomes in the relapsed refractory setting was actually a consolidation with transplant. Whether this is with blinatumomab, whether it is with inotuzumab, whether it is also with a competitor CAR-T program, the statements, when you look at it all across, is that you actually get to, we try to get an MRD negative state, a complete remission with an MRD negative state, and then try to actually do a transplant, particularly if the patient had to be transplanted before, as Claire was pointing out. So that was. That's pretty much ingrained in the field in the sense that that was one of the only ways you could get a longer-term outcome. I think what was unusual about the data that you just heard from Claire is that this is probably the first time that we see an outcome that did not get improved by consolidation with transplant. And I think that was actually, to us, actually a remarkable part of the analysis. When we ran the analysis, it was remarkable to see that indeed it does not improve. Now, there's a logic to that, and Claire pointed to that before, which is obviously that most of the patients that got transplanted in the study actually had ongoing persisting CAR T cells. Obe-cel was there, were still active. And by removing obe-cel through the preparation for the transplant, basically you lost the surveillance in these patients, and now the transplant on its own, you know, obviously has a limited ability to do that over time. And we believe that that actually led to this worsening of the outcome, to actually the patients that did not get transplanted and have the benefit from ongoing persisting obe-cel in their system. So but that, I think, is important. To my knowledge, certainly, and Claire, correct me if I'm wrong there, but to my knowledge, it's the first time that I think we see that indeed consolidation with a transplant as post one of these targeted therapies actually led to certainly no improvement, potentially a worse outcome. Yeah, no, I think that's right. I think, you know, I don't think anyone has definitively shown that transplant is improving the outcome for patients after CAR T, to date, and certainly not in this analysis. Okay. So maybe kind of following up on this and giving... Given the results that you've seen, especially with patients who have more than six months of cell persistence, do we envision a world in which, you know, transplant decisions are gonna be made based on T-cell persistence? Is this something you guys are gonna start monitoring, practically, when giving obe-cel? Yeah. So I mean, at the moment, there's actually, in the pediatric setting, there's a study ongoing, which is using the combination of sort of NGS-based MRD analysis with CAR T cell persistence, trying to sort of develop, it's almost like a sort of, you know, an algorithmic scoring system to be able to determine individual risk at a, you know, any given time point post-CAR T to help guide these decisions, because clearly, these are really important decisions to get right. So I think it will be sort of systematic evaluation of these, you know, the combination of parameters, CAR T probably plus a deep measurement of measurable residual disease to enable decision-making about consolidation or not in patients. That's very helpful. And the last one, the abstract reviewer yesterday was clearly very excited about the possible near-term addition of obe-cel, basically repeatedly said, "Hopefully, will be added soon. Oh- Is this the typical feedback you guys have been getting from physicians? From every walk of clinical practice, you know, because not least because it's just so... I mean, it's been so easy to give in terms of the toxicity profile. It's the sort of drug that you would consider for your older comorbid patient. You know, so in terms of the sort of, if you like, the burden to the patient, the burden to the patient's family, the burden to the hospital unit, you know, associated with giving this, and then you've got these lovely sort of long-term outcomes. By all means, across the whole adult sector, everybody's really excited. But the excitement also extends into the pediatric sector. So for instance, you know, the investigators across the U.S. are really sort of pushing hard to enable access to obe-cel for their pediatric patients with ALL as well. So I think, you know, maybe people are watching the adult data with great excitement and, you know, imagining the use of it even more broadly. Christian, you probably would have something to add to that. Yeah, I think it's really resonating very well, also in all the regional lab boards that we have been running across the US with physicians who have not been part of the FELIX study. The study does resonate remarkably well. It is, it's a sort of a real-world population that's represented in the dataset, including, you know, very challenging patients, like patients with extramedullary disease, and ones with isolated extramedullary disease, you know, can certainly tend not to be included in clinical studies. So there is a way to actually see the patients reflected in the data that the physicians are seeing in their own practice. And I think that it certainly has resonated a lot. The safety profile, as Claire said, is something that's immediately experienceable and have a huge impact on the hospital, it has a huge impact on the patient. And I think there is also a sense that products that are actually easier to manage, that you also have an ability, frankly, to treat more patients, because the resources are not quite as strained as if you have a product that actually requires a lot of attention to be managed. So those are certainly key feedbacks that we've been receiving and I think are very consistent with what Claire just walked us through. All right. Thank you very much for taking our questions. Thanks, Gil. Thank you. One moment, please, for our next question. Our next question comes from the line of Asthika with Truist. Hi, good morning, everyone. Thanks for taking my questions. I have a few, if you don't mind. So let me ask in a couple of clusters here. Dr. Roddie, I echo Gil's question here, or reflection that the discussant was very excited about this data. So I just want to ask you point-blank: Is the sample and the strength of this data enough to be immediately practice-changing? That's one. And then in the likely scenario where you have both obe-cel and TECARTUS at your disposal, what is the use case for TECARTUS? And then a third quick one there, if I can add, to you, Dr. Ode, in high tumor burden patients, so the ones with greater than 75% blast, what else could you be consider using to get similar results as obe-cel? And then, Christian, I got a couple of quick ones for you, too, after. Okay. All right. Claire, do you have them? Yeah. Well, so in terms of the—I mean, is it practice-changing with sort of immediate effect? You know, I think the answer to that is yes. I mean, this is the biggest study in adult ALL of CAR T therapy. I mean, we treated 127 patients, and I think, you know, these kind of Kaplan-Meier curves speak for themselves, really. So, I think in answer to that, yes, and hence the excitement across the U.S. and the reception of the abstract yesterday. In terms of sort of decision-making between products, and again, you know, I think I've sort of voiced this on previous calls, you know, it is to some extent like night and day. And, you know, this is by far and away, you know, an easy, an easier-to-deliver product. It's associated with the, you know, the long-term outcomes we've discussed in the slides. It opens up CAR T therapy to a whole new population of patients who you would never consider for brexu-cel. You know, those, as I've mentioned, those older and those comorbid patients. You know, it just so. So it basically is giving an opportunity for therapy to patients who otherwise wouldn't be considered. So I think, you know, on those two fronts alone, you know, it's just, it's a massive, massive development in the adult ALL field. In terms of patients with more than 75% blasts, again, you know, we, I mean, we, obviously, we've seen the data, and we know from across the board, CAR T therapy and other therapies, that these can be a difficult patient population to manage. Again, you know, it'll be different depending on which physician you ask as to what approach one should take. I've certainly got patients in my practice who've had more than 75% blasts, who have got durable long-term responses following, you know, obe-cel in the context of both phase one and in the FELIX study. But there are other patients who, you know, who have lost their responses. So I think we watch those patients very closely, and we certainly consider if they are eligible potentially for, you know, they haven't, they're allo-naive, let's say, you know, that they would be the kind of patient who you would counsel about the pros and cons of watch and wait versus consolidation therapy. That decision is heightened if, for instance, they lose their CAR T engraftment or, you know, they reconstitute their B cells. I mean, I think that decision then becomes easier to make, but, you know, it's always a balance because, you know, the sort of head-to-head data of allo versus CAR T watch and wait, it's just not there. You know, we always are sort of having to try, to try and piece together the kind of retrospective data to sort of answer this question. It's never been prospectively studied. But yeah, they are a higher risk group, and we do, we do watch them with great care and very closely. Christian, would you add to that? I think that's right on. I think, Asthika, you had an additional set of questions you were mentioning. Yes, and Dr. Roddie, maybe just fine-tune on this question. Is there a use case for TECARTUS if you have obe-cel at your disposal? Sorry, is there a what case for it? Sorry, did you say? Is there a use case? Like, is there any type of patient that you say, "Yeah, yeah, this is the kind of patient I would actually use TECARTUS in over obe-cel? If there is, I can't think of it right now. Okay. Okay. Thank you, Dr. Roddie. That's really helpful. Christian, so I wanted to just set up, check in with you on the persistence and efficacy that this, that this data really, links together quite nicely. One, how do you use this, in your further development of obe-cel in, this, this knowledge that, that the persistence is, is now, tied to efficacy? How do you use this in your further development of obe-cel, in other indications, as well as other CAR Ts at, at Autolus? And second, did you look at the evolution of the dominant, clonotype of the CAR T cells over time? I'm wondering if this is dynamic or if there any specific groups that persist and are potentially what's driving the long-term efficacy. If I can squeeze a quick question in on the autoimmune study. If you could give us an update on number of patients, recruited, that would be great. Thank you. Yeah. So first of all, I would say the fact that persistence, you know, has a significant impact, particularly in acute leukemia when it comes to longer term outcome, is obviously something that we knew about it for a long period of time, and actually were a deliberate property that we're looking to design into obe-cel. I mean, the early information, obviously, that persistence matters, particularly in pediatric ALL patients, came from the work that was done by UPenn in KYMRIAH, that showed that indeed, the kids that had long-term outcome also had long-term persisting CAR Ts. We then actually, when we were doing the initial work, with our colleagues at UCL in the CARPALL study, obviously did see that also the children that actually had long-term outcome and got a cure, also had long-term persisting CAR T cells. And in that context, we did see CAR T cells measurable and actually could be followed by flow, in blood from these patients 3-4 years out. Now, one of the things that you may remember that of those patients, we had an ability to actually analyze what the composition was of those CAR T cells, what were the features of the CAR T cells. And what was quite striking was that there was a typical clone that was sort of surviving longer term of the CAR T cells. In fact, when we looked at those CAR T cells by flow analysis and looked at the various differentiation types of these CAR T cells, actually looked pretty much in terms of composition of what the original product looked like that went into these children. So that's where we have actually a lot of information from that pediatric study we did, longitudinal work, and part of that is published. So it very much, I think what we see is really that's a property that actually encompasses all of those practically the entire product, and the product seems to be represented over time in a distribution of which is actually very, very similar to what the original product looked like that was manufactured before and reanalyzed before infusion. So those are kind of a few thoughts on persistence. Obviously, we continue to work, and we continue to follow these patients. And I think there's a lot more that we will learn over time, as we sort of take a deep dive in the product characteristics versus outcomes. And that's a key analysis that we're now actually going through. And I think there's opportunity for additional updates as we go forward that look at those, possibly also mechanistic type of relationships that we might actually find here. So still a lot to analyze. I think we have a good sense, and we did from the get-go, through the pediatric work on the importance of persistence. We start to learn, obviously, now with this, very sizable data set, have now an ability to really start to ask these, these much more multivariate type of questions, for, you know, patterns, et cetera, that may actually impact, outcome. That's an area of very active engagement, and then certainly we'll continue to do a lot of work in that, in that area. Then the final part was, you were asking about how we're doing with the SLE study. We did, I think, just a very recent call in the Q1. Our recollection is that we told you that we had the first two patients enrolled, and obviously very active on that side, and, gave you, indication that we expect data from that study by the end of the year. There's nothing that's changed in that outlook. Thank you. One moment, please, for our next question. Our next question comes from the line of Kelly Shi with Jefferies. Well, thank you for taking my questions. I'm just curious, in the 40% of the responders in the ongoing remission without transplant as follow-up, the proportion of the high-risk patients is similar to that in all comers? Claire, do you have that? Well, so- Uh. So what was that? Pardon me. In the guys with the 75% blasts, was that, was that the question? Or were they adequately represented in the 40% long-term responders? In the 40% of long-term responders, the high risk patients, in a similar proportion to that in all comers. I mean, I don't have that data to my fingertips, but, you know, obviously, there were a higher proportion of those patients with the sort of over 75% blasts, who unfortunately did lose their response sort of at the earlier time points. So, you know, obviously, we do recognize that the kind of that superior EFS curve, I think maybe Christian showed it earlier, you know, that sort of correlates with the, you know, the lower disease burden. You've got the difference of when you subdivide it according to disease burden, you can see how that impacts EFS. So yeah- Mm-hmm. So proportionally, I mean, you are more likely, I think that goes without saying, you are more likely to achieve the long-term remission in those sort of lower disease states. But I think that that's not unique in this context. This is not unique to FELIX. This is something that has been, you know, reliably sort of seen across all of the different CAR T cell therapies, Tisa cell in children, and it's been seen in ELIANA in Spain. I mean, it's just, it's a sort of, it's a, it's just the paradigm unfortunately, there, you know, high disease burden does confer that sort of slightly higher risk of losing response. One other element to add maybe, Kelly, is that, in the slide that I presented at ASCO, kind of the impact of tumor burden at lymphodepletion. So I think what we see is a reflection of that, in the data. So it is not necessarily the tumor burden at inclusion that actually determines that outcome, but it's the tumor burden at lymphodepletion, which then also gives you the information about the nature of the disease, the progressiveness, the speed at which the disease actually progresses, and your ability to influence that. That actually is kind of the added information that you get at lymphodepletion because you had exposed these patients, most of them, the more than 90% of the patients had been exposed to bridging therapy. So you actually get an information there that is actually very valuable, and, as Claire was saying, there's obviously a buildup and obviously a weighting towards patients that have lower levels of tumor burden at lymphodepletion in that 40% bucket. Yeah. The beauty of bridging, obviously, I mean, with evolution and bridging practices, you know, there is the potential for us to modulate the disease burden coming in. So, you know, we've had some degree of success with drugs like Inotuzumab, you know, and sort of quite dramatically altering sort of disease burden between screening and lymphodepletion. So I think as we sort of become more knowledgeable in the space and we, you know, like, I think we're going to be able to sort of improve burden at lymphodepletion in an increasing number of patients with better bridging practices. Super helpful. Thank you. Thank you. One moment, please, for our next question.... Your next question comes from the line of Sebastiaan van der Schoot with Van Lanschot Kempen. Hey, good morning, team. Congrats on another strong update. There was clearly a lot of excitement yesterday at the presentation. I am wondering whether you can provide some insight into the dynamics of between loss of CAR T persistence, B-cell recovery, and subsequent relapse. What are the time windows between those events? And if CAR T persistence is lost, is that more of a gradual effect, or is it immediate? And when would you then still consider doing stem cell transplant? Thank you. Okay, Claire, do you want to take that? Well, so, in terms of the, I mean, 'cause it's again, this is such an important sort of area of study in the field. So, you know, I don't, we haven't formally reviewed all of that data to present it, yet, sort of the chronology of these things, and that will be the focus of sort of a subsequent update. But, you know, what we know from sort of other settings, so for instance, Pulsipher, who looked at the NGS MRD evaluation in pediatrics, you know, 'cause then it depends on how you're sort of measuring your disease recrudescence, really. And so if you can get the sensitivity of detections down to sort of 10 to the minus 6, sort of reliably, then, you know, those are... That's going to be particularly valuable data because it gives you sort of like an early snapshot, potentially, of someone who is inevitably going to relapse. So I think, you know, the modality by which you choose to look at your sort of disease burden, it's going to give us more opportunity to be able to salvage patients, so using the likes of MRD. But I think, you know, putting all of this together, putting all of these parameters together, is going to be the focus of another update with those timelines. Christian, is that fair to say? I think Michael's working on that data at the moment, isn't he? Absolutely. Now, one of the things that I think we can say is, Sebastian, we obviously do have a pretty good understanding of some of that dynamic from the phase I experience, both in the CAR-19, the old CAR study. And I think what is fair to say is that we can see a sequence, and the sequence tends to be, loss of persistence, followed by recovery of B-cells and then leukemic relapse. And I think that is a sequence that we see quite consistently. Timing is variable with that, but I think as a sequence, that is certainly something that I think we have seen. The only exception is when we actually have a patient that has a CD19-negative relapse. In that case, we could still actually have persisting CAR T-cells, but the relapse, and the B-cell is not coming back, but the relapse actually starting to occur. Mm. So that's the only exception to that. But in a CD19-positive relapse, we tend to see that sequence of loss of persistence, recovery of B-cells, and basically, the leukemia coming back. But to Claire's point- Okay. We're looking at that across more systematically across data set at work. Okay. And if I can ask please one more question. I think you mentioned that the prior lymph conditioning therapy can remove CAR T-cells. Is that only seen in a proportion of patients, or is that in all patients who receive stem cell transplant treatment? So, what... Sorry, the conditioning therapy for the transplant is, obliterates the CAR T-cell engraftment? Yeah? Is that what- Yeah. that's the question? Yeah. Is it in all patients or in a proportion of patients? Well, look, again, you know, that, that is also the focus of ongoing analysis at the minute. So we're looking at the impact on CAR T-cell engraftment in the patients on this particular study, who underwent subsequent allo transplant. But, yeah, I mean, the conditioning is still profound. So, allo transplant usually engages sort of T-cell depleting chemo immunotherapies. So the experience in that across the field in CD19 CAR T is that it does obliterate the CAR T-cell engraftment. So, but again, you know, within the FELIX study, that's a piece of analysis that's ongoing at the minute. So to look at and to compare, and to look at those patients who had those allo transplants and to look at the marking afterwards. Okay, great. Thank you so much. Thanks, Sebastian. Thank you. One moment, please, for our next question. Our next question comes from the line of Matthew Phipps with Blair. Good morning. Thanks for taking my question. Congrats on update and, you know, continued durability and persistence there. I guess, I'll ask about kind of commercial prep. You know, maybe you can just give us a little insight of how many centers you feel like you're kind of prepped and ready to go at launch, and maybe just like cadence of expanding those centers in the US. Also, maybe when you can go to that second manufacturing, you know, sub-facility, whatever you want to call it. And then lastly, any cadence on kind of payer reimbursements and NTAP payments? Yeah. So, so first of all, thanks for, for joining, Matt. I think, with regards to, to the preparation towards commercial launch, obviously, this is a, an area of very heavy activity. There's obviously, one, key, aspect of the activity is what's going on at conferences like this conference here at ASCO. In Chicago, which is really, engaging, with the treating physicians and, and really make sure there's a high degree of awareness around the program. So it's a very intense medical affairs program ongoing. The second area is really, getting the centers ready to be in a position where they can actually, once the product is approved, can actually, offer the product to patients. And one of the key things that obviously is relevant, it's important there is-... have to be licensed to use a product, a CAR T-cell product. That's quite an involved process, and actually requires a very significant amount of engagement with the centers. The centers obviously need to go through, there's a lot of aspects related to training. There is aspects of how you manage the product once it's on the center, the physical handling of the product. But also, the collection of longer-term data in the context of the REMS program, which are all components that obviously are relevant. In order to support all of these activities, including support. In order to support that, there's a very significant level of IT support required. There are platforms that we're using that actually help with the orchestration of the product, product flow, making sure that there's visibility on where the products are, and there's planability at the centers of when to actually get the patients back in, prepare the patients for infusion and so on. This is a very involved process. There's also a lot of contracting work that is required because all of these aspects need to be tailored to the specific center. Typically, you look at it at a time between about 6-12 months of work with each one of the centers on where they are then ready, that once the approval comes through, can go to the final steps of activation. So we expect at the time of the PDUFA Date, that we should have somewhere in the range of 30-36 centers in a position where we can do the final step of activation once the approval is through. Then build very rapidly from that 30-36 center number up to about 60 centers that we expect to have as a key target to reach in the U.S. We would actually go on an almost continuous basis forward and really make sure that we actually get to that level in a relatively short period of time during the course of the first year of launch with the product. So that should put us in a position where we should be able to reach somewhere in the range of about 90% of, or have an ability to access about 90% of the patients that are treated at that stage of their disease in the US. Thank you. One moment please, for our next question. Our next question comes from the line of James Shin with Deutsche Bank. Hey, good morning, Christian and Claire. Thanks for taking my question. Just wondering, are preliminary rates for relapse and non-relapse mortality available? And then for FELIX, is there a breakout for OS by patients with and without prior Blincyto exposure? And then, Christian, the 30-36 centers that should be online, that's just U.S. Is there any E.U. facilities included in that number or no? Yeah. Beth, you want to clear on the analysis? So, in terms of the treatment-related mortality on study, is that right? So that, because that was the subject of, you know, of our prior sort of toxicity updates. And, you know, as you're aware, obviously, the immunotoxicity rates were really low, and the rates of sort of vasopressor use were really low. It was like 2.5% or something like that, of all patients. And there were only a couple of deaths on the whole study that were felt to be treatment related. So I think, you know, the TRM on study was actually really low. In terms of the blin versus no blin, so again, that's a piece of analysis. We've got sort of like a team of statisticians looking at all of these different parameters that may impact upon outcomes. You know, we obviously looked at a, there was a forest plot previously of people who'd been previously exposed to blin versus not. And there really, it wasn't a very marked sort of difference in kind of likelihood of achieving CR, whether you'd have been pre-exposed to blin or not. But we are conducting some analysis to look at sort of CD19 expression levels, you know, pre-treatment based on prior blin exposure. So I don't think blin's coming out as being a sort of like a massive sort of... It's not massively impacting upon your likelihood of achieving CR. I'm not sure. Was there another part of that question was for me, or was it just the blin and the TRM? I think those were- No, that was- - the key questions. Okay. Yeah. The other question was for when Christian was mentioning the 30-36 centers. Mm-hmm. Did that include any European facilities? No, actually, the focus obviously at this point is really on the U.S. launch, and that's going to be the centers that I did quote, up to 60 centers only. The approval in the U.S. is ex- in Europe, is expected sometime during the course of next year. Obviously, the process is somewhat different from the review process that the FDA runs. And would then actually allow us to initiate the launch in Europe. The thing with this is you have a country-by-country launch in Europe, and we're in the process of actually running through the sequencing of the countries. Essentially, we'll provide more of an update at a later time point. But then quite usually, if we look at it at a launch sequence in Europe, it tends to start in Germany, France, and then actually and obviously, one of the key areas for us also, being as a U.K. company, is also to have a drive towards a U.K. approval and a launch in the U.K. So, both of those, you know, we're hopeful that this can actually be happening through the course of next year while we're sort of ramping up the activities in the U.S. Now, there's one question that Matt actually asked before that I didn't answer, and I just recalled. One of the things that I think Matt asked was related to potentially having an NTAP, which is a new technology add-on payment. which is basically an ability to support new therapies or including options into these settings for a subset of the patients that are supported by the U.S. government. That's a process that tends to be an annual process, and so we certainly would expect that we would apply for an NTAP once the product actually has gone, has reached, received. And that actually could provide an added level of support for the treating centers, and then sort of an improved level of reimbursement for the treatment centers as part of that scheme. So that's just as a follow-up on Matt's, I think, second part of the question that I didn't answer before. Thank you. One moment please, for our next question. Our next question comes from the line of Yanan Zhu with Wells Fargo. Great. Thanks for taking our questions. Wondering about, in terms of, the analysis for censoring versus not censoring, the subsequent stem cell transplant patients. Has that kind of data and analysis also been done on TECARTUS's ZUMA-3 study? If so, its outcome generally is similar, or could a stem cell transplant have a differential impact, following TECARTUS? Well, to be fair on the... I mean, the ZUMA-3 study, there were a total of, like, 10 patients were consolidated with an allo transplant or received an allo transplant. That was 18% of all of the patients on that study. They showed that the median sort of duration of response was similar. So I don't think that they saw, you know, like, a massive benefit to consolidation with allo transplant either in that setting. So I... Yeah, I'm not sure, Christian, if there's any other aspect that you would want to highlight there, but yeah, that's my experience. I think, well... Right. So when you look at the ZUMA publications, what you do see, and what was highlighted there as well, is that there was a somewhat of an improvement. See, it was not a big improvement because the number of patients that received the transplant was limited, but the curve was running somewhat better. So above the overall curve, different obviously from what we were observing, where our curve at post, or with the transplant, it actually runs below the curve without a transplant. So there was a difference there. It wasn't huge because obviously the number of patients that got transplanted were very limited. But certainly in some of the sub-analysis that were shown over the last few years, sort of indicated that, at least there was a sense that these patients did better. And it was also, I think, probably reflected in the summary of the ROCCA study presented at ASH at the end of last year, where the presenter concluded that the recommendation was that the CAR T therapy should be consolidated with another therapy, one of which obviously would have been stem cell transplant. And similarly with the outcomes when you look with Blincyto, clearly long-term outcomes, the patients that actually were consolidated with stem cell transplant long term actually had a better outcome than the patients that did not get consolidated, from an overall survival perspective. So there was a difference there that was visible as well, and it was a bridge to transplant, one of the key uses of Blincyto. And, you know, similar to what I think Claire Roddie showed before in terms of general practice. Got it. That's super helpful. Then also, I was curious about, the, you know, when using CAR T persistence as one of the parameters to, predict outcome and, intervene with, stem cell transplant if necessary. I was wondering what might be the right time point? Looking at the graph you're showing, for the six months, looks like patients could progress, pretty quickly between six and nine months. A substantial portion of the, relapse happened during that three months. Do you think the six months, persistence will still be timely enough to implement, intervention to prevent, those relapses? Thanks. Yeah, I mean, it's an interesting point, isn't it? It sort of comes back to the kind of question that was asked earlier as to, you know, what is the sort of time interval between the kind of loss of CAR T persistence, the recrudescence of your B-cell compartment to the sort of relapse. And I mean, clearly the data is what it is. I mean, there's clearly a, like, an EFS benefit, if you've got ongoing persistence at month six, but, you know, nothing is absolute. And so there will be that sort of risk of patients sort of dropping off. You know, it just depends on where you cut the curve, you know. And six months seems like a reasonable time point to do that. I think as we sort of move into the kind of field of, you know, the use of NGS methods of MRD detection, it will give us the opportunity, if we do get those patients losing CAR-T persistence, and then if we're using that test in conjunction with sort of like a deep and sensitive measure of MRD, we should be able to sort of, you know, make kind of, you know, consolidation decisions before the point of frank relapse in those patients as well. So I think, you know, the kind of the combination of measures is going to be what's going to be most potent in terms of helping us, you know, guide consolidation before patients frankly relapse. Got it. Got it. Thanks, Dr. Ratti. Thank you. One moment please, for our next question. I'm showing no further questions. With that, I'll hand the call back over to Christian Itin for any closing remarks. Well, thank you very much for joining everybody. Really appreciate you taking the time. Particularly, we'd like to thank Dr. Claire Roddie for joining us today and sharing her insights on the study and the treatment paradigms within this tough to treat indication. So looking forward to keeping you updated. Really appreciate your time today. Thanks a lot, and have a great weekend. Ladies and gentlemen, thank you for participating. This does conclude today's program, and you may now disconnect.