Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autolist Therapeutics call to discuss its full year 2024 financial results and business updates. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Amanda Cray. Please go ahead.

Thank you, LaTanya. Good morning or good afternoon, everyone, and thank you for joining us on today's call. With me, our Chief Executive Officer, Dr. Christian Eiten, and Chief Financial Officer, Rob Dolski. I'd like 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 status of the ongoing commercial launch of Ocassel in the U.S., auto list manufacturing, sales, and marketing plans for Ocassel, the market potential for Ocassel, and the status of clinical trials and development and or regulatory timelines for OB-Cell and our other 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. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and in our SEC filings, both available on the investor section of our website. On slide three, you'll see the agenda for today's call. As usual, Christian will provide an overview of our operational highlights. Rob will then discuss the financial results, and Christian will conclude with upcoming milestones and closing remarks. We will then take your questions. With that, I'll turn it over to Christian.

Thank you very much, Amanda, and welcome everybody to our fourth quarter 2024 financial results update. So first off, obviously, we had a very successful 2024, which sets us up well for the 2025 that we're already in a few months now. First of all, I'd like to just highlight kind of the key objectives that we have for the year. So the primary objective clearly is to execute a successful commercial launch for a capsule, and we're doing really well and advancing well on that. We'll provide a bit of an update as we go through the presentation. But also, we see a lot of opportunity for OVCell to actually expand its utility, the excellent profile that we've seen in our current experience with the product, and explore the opportunity and additional indications, as well as look at the opportunity for moving some of our other product candidates forward And at the same time, obviously, we'll be, I think, very selective and very careful in how we're going to place our investments. Now, one of the things that you'll hear us also briefly mention is the fact that we're planning for an R&D event on April 23rd in New York that will actually outline in more detail kind of the plans on how we want to move forward in sort of creating additional opportunities for future growth. So with that, on the next slide, I believe we're going to summarize kind of the key opportunities that we have seen and sort of achieved during the course of 2024. As I mentioned, this has been a remarkably successful year, and we had a very strong start of the year in the first quarter when we were able to add about $600 million to our balance sheet through our collaboration with BioNTech as well as a public financing that we conducted in the first quarter. This set us up very well to really be able to focus fully on making sure that we get OBSEL already to get through the approval process in the US, but also to set us up well for the commercial launch of the product. As we're going through the year, I would say we had continuous activities on the commercial side to actually get the sites ready. so that they actually would be in a position, once the product was approved, to actually start onboarding the product and be in a position to move forward and actually use the product in the commercial space. Now, when we look at the approval itself, we achieved the approval in the US on November 8. And I think what was very encouraging was that not only did we actually achieve the approval slightly ahead of schedule, but also actually had a label which gives us a broad opportunity in the relapsed refractory ALL space for adult patients, and actually having the first product getting through the approval process that actually did not require a REMS program. Very nice setup in terms of the approval itself, the timing of the approval, not having a delay, recognizing that the product had an attractive safety profile, and therefore no obligation for collecting additional information around CRS and ICANNs going forward. And that actually is, I think, a very, very strong foundation. What was then very, very helpful is that we were able to actually get the clinical results published in the New England Journal of medicine in the early part of December and shortly thereafter the product was included in the NCCN guidelines. This is very important as you start launching a product because it gives obviously a lot of confidence and indeed this is a recommended therapy and also will support the decisions that payers have to obviously go through to get the patient signed off for commercial use. When we look at the track that we had as we went through the first three months of the launch, we see a very good development in terms of the number of centers that are actually authorized and are able to deliver the product. We're currently showing 33 centers that are authorized as of March 19. And we expect that that group of centers allows us to reach approximately 60% of the target patient population in the US. We are continuing to move forward, adding additional centers as we go through this year. By the end of the year, expect to have approximately 60 centers that will be ready and in a position to deliver Ocacil to patients. We believe that those 60 centers actually reach the vast majority of the patients in the U.S. and will give us a very strong foundation for a successful delivery of the product to the patients across the U.S. I already mentioned that we obviously have the publication of the study, of the Felix study in the England Journal, but we're also, in addition to obviously getting ready for launch in the U.S., we're also moving through the regulatory steps in the U.K. and in Europe and had filed in the early part of 2024 with EMA and then by middle of the year with the MHRA. And we expect actually regulatory decisions in the second half of 2025. We also started the process to actually establish ultimately the utility of the product in the UK and we're going through the assessment. by the National Institute for Health and Care Excellence, or NICE, which is one of the key processes that you have to run through to get to a position to actually get a product adequately reimbursed in the UK. As we went through the year, there were several data presentations at key conferences that really focused on the properties that we have observed with a capsule or OV cell in the relapsed refractory adult population as we were going through and sort of actually gained more and more data from the Felix study. We could report on the durability of the product, highlighted the safety profile, the impact of having deep molecular responses and persistence as indicators and likely requirements to get to long-term outcomes with the patients. And we also actually were able to show the impact of tumor-verted guided dosing, as well as the safety profile's impact on reducing health economic cost when we look at the cost of treating the patients. So quite a comprehensive data set that we actually were able to share across a range of conferences during the course of last year, including the tandem meeting in February this year. Moving to the next slide, we're looking briefly here at some of the key outcomes that were actually presented and published in the New England Journal publication. And what we're seeing is that the product has a very high level of clinical activity reaching deep molecular responses in the majority of the patients. And that type of activity obviously has come with an attractive safety profile that we can see that overall the level of high-grade cytokine release syndrome and the level of high-grade neurological toxicity or ICANs are low. And in fact, when we look at patients that have low levels of disease burden at the time of dosing, those patients did not experience high-grade events, either CRS or ICANs, which I think gives us a good understanding of patient profile and also kind of from a safety perspective. And as we're looking at the next slide, we also see that the tumor burden also actually gives us important information about the impact of the therapy it can have in terms of longer-term outcome. In this slide, we're looking at event-free survival. As you can see in the top part of the panel, event-free survival stabilizes at around between 45 and 50 percent. And we see that the line actually is starting to go horizontal, indicating that there is a proportion of patients that do not actually seem to progress or actually have events that are occurring. When we look at what the impact is of the disease burden prior to dosing, we can see that patients that have low disease burden, less than 5%, do remarkably well. Whereas most patients with a wide range of disease burden up to 75% actually continue to do very well. And only the patients that had extremely high levels of disease burden of more than 75% of blasts in the bone marrow at the time of dosing obviously have a lower outcome. So overall, I think, gives us a lot of information about the properties of the product. We have just talked about the safety that we've seen across the board, obviously the efficacy from an event-free survival across the board, which looks very attractive, and also there the impact of actually treating patients when the disease burden is still at a lower level, which gives us a very good prognosis for these patients. When we look at the next slide, we see that translating into overall survival, and we see the same overall picture, again, stabilization of overall survival in the overall population, and as well an impact that we see in terms of tumor burden, where patients, again, with lower tumor burden at lymphodepletion, and also patients with extremely high levels of tumor burden actually have a poorer outlook. Overall, remarkable set of data and I think sets us up for a very, very attractive proposition for patients in this field. Moving to the next slide, as we're sort of thinking about sort of the early momentum of the launch in the US, indicators here is the centers that can actually actively deliver products to patients. As I mentioned, we reached 33 centers on the 19th of March, which gives us obviously a very good reach and distribution already across the U.S. and obviously a presence in a lot of the more densely populated parts of the U.S., which is also the reason why we're already reaching more than 60% or around 60% of the patient population. What's also important is we're making good progress in terms of patient access, in terms of lives covered, and we see actually very good momentum there as well as we have been going through the last three months. So that is very encouraging and also actually is a good sign that indeed patients do have really an opportunity here to get access to this therapeutic option. Finally, on the next slide, on the update, you have heard us actually talk quite a bit about the actual manufacturing facility for commercial supply, which is the nucleus facility. I think one of the remarkable things about this field is obviously as you have the first commercial patient come in, that's when you literally start the operation at that facility. And I think at this point we can say that we're off to a really good start and the facility came to life and is humming well and I think will give us a very strong foundation in our ability to reliably deliver product to the centers. So with that, on the next slide, which is really focusing on the expansion of the OB cell opportunity, a key area that obviously we're going to be focusing on in 2025. First off, on the autoimmune side, we've been running obviously the Carlisle study. We have the initial cohort of six patients that are all dosed. We're running through the data cut for the upcoming R&D event on April 23rd. And we're looking forward to updating you on that initial experience with the first six patients. And we also are planning to present the data with long-term follow-up across the patients at a later time point in the second half of the year. On the hematology side, obviously we also have been moving forward with our pediatric study, the PY1 study, and we expect to provide an update also second half of the year. That study has also been evolving very nicely. In terms of the early pipeline, we obviously have a set of activities ongoing with our partners at the University College in London, and we are moving forward or have been active in Auto 122, Auto 6 and G, and Auto 8, and we continue to progress the activities around those programs, collecting more information around the programs and are planning to also give a short update at the R&D day towards the end of April. So with that, I'd like to actually hand over to Rob and give us a summary of the financial results.

Thanks, Christian. And good morning or good afternoon, everyone. It's my pleasure to review our financial results for the full year 2024. Cash, cash equivalents and marketable securities at year end 2024 totaled $588 million as compared to $239 million at the December 31st, 2023 timeframe. This increase was primarily a result of our strategic collaboration with BioNTech and concurrent equity financing for a combined $600 million in gross proceeds to bolster the balance sheet ahead of our U.S. commercial launch for OCATSL. Loss from operations for the year ending December 31, 2024, was $241.4 million as compared to $179.7 million for the year ended 2023. Cost of sales totaled $11.4 million following the BLA approval for OBSEL. This amount represents the cost of commercially available plant capacity that can no longer be classified as R&D expense as of November 8th, OBSEL's approval date, even though it was not associated with product sales in the fourth quarter. Our research and development expenses increased to $138.4 million for the year-end in December 31, 2024, compared to $130.5 million in the same period, 2023. This change was primarily driven by increases in employee salaries, related costs, manufacturing costs related to OB-Cell, and then partly offset by some decreases in professional fees and facility costs. Our selling, general, and administrative expenses increased to $101.1 million for the year compared to $46.7 for the same period in 2023. This increase was primarily due to the salaries, other employee-related costs driven by the overall increase in headcount supporting commercialization activities. And finally, net loss was $220.7 million for the year ended December 31st, 2024, compared to $208.4 million for the same period in 2023. With the recent approval of a CATSOL in the U.S., I'd also like to note two financial milestones that were triggered in the fourth quarter. As a result of the FDA approval, Autolist received a $30 million milestone payment from Blackstone based on the terms of our previously announced Blackstone collaboration agreement. In addition, the company made a regulatory milestone payment of 10 million pounds sterling in accordance with our UCLB license agreement. These are both detailed more specifically in our 10-K filing. We continue to believe that with our current cash, cash equivalents, and marketable securities, we are well capitalized to drive the full launch and commercialization of Obicel in relapsed refractory adult ALL, as well as to advance our pipeline development plans, which includes adequate runway to reaching data in the first pivotal study of Obicel in autoimmune disease. And as Christian noted, we look forward to providing further detail on these plans at our upcoming R&D event. I'll now hand back to Christian to wrap up with a brief outlook on expected milestones. Christian.

Thank you very much. And moving to the upcoming milestones. So when we look into 2025, We are starting the year with also the update on the SL1 Carlisle study, which we are planning to provide on April 23rd at the R&D company R&D event in New York. We then, when we look at the pediatric study, expect to provide the update on the pediatric study second half of the year, as well as obviously longer-term follow-up on the Carlisle study as well, second half of the year. And we do expect also during the second half that we receive the notifications around the regulatory process for the UK as well as for the EU regarding potential approvals in those two jurisdictions for OBSEL. So I think a very interesting year for us in terms of the progression of opportunity that we're actually starting to execute on. We're outlined at the company R&D day. But then also, obviously, we'll be able to provide more evidence and projections as well with regards to the launch progress that we're making for a capsule in the U.S. So with that, we're happy to take questions, and we'll hand over to the operator. Thank you.

Certainly. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. to withdraw your question, please press star 11 again, and please stand by while we compile our Q&A roster. One moment for our first question. Our first question will be coming from James Shin of Deutsche Bank. Your line is open, James.

Hey, good morning, guys. Thank you for the question. On Ocatil's launch, and I know it's a progressively evolving situation, can you provide any color on the initial demand or the book of orders thus far? And then secondly, Oncologists have mentioned that the split dosing and the delayed onset of CRS oral capsule can be useful for outpatient administration. Can you say whether outpatient use is happening or planned thus far? And I'll just leave it there.

Yeah, well, first of all, thanks a lot for joining, James. On the launch, I think what we can say is that we have obviously seen a very nice dynamic around the actual activation of the centers, which is really critical. And it's very much driven by the level of interest, enthusiasm by the centers to actually do that work and actually get the product active. That also is often driven by actually having patients that are in need of therapy, which is sort of usually actually the key driver in that process. So I think that gives us a very good level of confidence in terms of how the product is viewed, the level of interest, and I think the dynamic we've been seeing has been very encouraging. Obviously, we provide a fuller picture at the Q1 update, but I think what we can say is that we see a very good dynamic and I think a very significant level of interest and I think a recognition that the product has attractive properties. for these patients. With regards to the outpatient question, I think there's an opportunity, as you've seen from the safety data that I highlighted during the presentation, is that patients that have very low levels of tumor burden at lymphodepletion tend to have a very limited amount of immunological safety events. And I think that is certainly attractive and has led to a number of physicians to suggest that they might be interested to actually explore and possibly to administer the product in sort of a hospital outpatient setting. We'll need to see how that evolves. A lot of that has to do with the actual experience gained with the product on the commercial setting and the confidence physicians are building up. And I think we'll see that evolve over the upcoming periods. I don't think at this point in time I think we can guide you in any way at this point. I think it's too early in the launch. But it's clearly an observation that a number of the physicians certainly have made. And it will be interesting to sort of follow that as we go through the year. Thank you.

One moment for our next question. And one moment for our next question. Our next question will be coming from Rajan Sharma of Goldman Sachs. Your line is open.

Hi. Thanks for taking my question. It's just a couple on logistics actually. So obviously you have the target to have 60 authorized centers by the end of the year. We're just interested in the ramp to get to that from where you are right now. Should we expect that to be linear or are there kind of, could this potentially come in in blocks of centers coming online? And then the second one, just on tariffs, actually, that's obviously been a focus for investors in the sector, given the headlines we're seeing. Could you maybe just talk to how you think that could potentially impact, given that manufacturing is in the UK? Thank you.

Yeah, thanks a lot for joining. So the first question is related to the ramp up of the centers getting online. I think we've seen in the first 30 centers, I think a pretty steady trajectory of these centers actually getting online, which I think has been expected because we do have a, we didn't have the 30 centers prepared for onboarding by the time of approval. And then it's the activation step that they were running through. And you could see that basically that we had Early January, as we had reported, around 20 centers that were active, and then that obviously built then through the quarter to now middle of March to about 33. So there's a pretty continuous kind of flow and movement that we've seen. With the next 30 centers, I think we'll see that build gradually as we go through the year. It's obviously very much, a lot of that is really driven by the individual centers and the time and the speed at which the onboarding process is sort of conducted. A lot of that has to do with legal reviews and so on. And frankly, the capacity at the respective hospitals to sort of manage that workload. So there is an element of variability, but we would assume that we have sort of reasonably steady process as we go through the year. And we obviously, you know, we'll be able to keep updating you on a quarter by quarter basis. And also the actual centers obviously are visible for physicians and patients on the autolysis website. So it is something that actually is, you know, can actually be followed. But in terms of projection, we would expect that to go relatively steady as we go through the course of the year. With regards to tariffs, I think very much an open question at this point in time, whether there will be tariffs, what it might be, what type of products might be impacted, et cetera. I think very hard to speculate. In most other, I think in the past, if we look at tariffs that sort of were imposed on pharmaceutical products, They tend to actually, you know, be very, you know, well thought through and typically minimal because nobody wants to actually have an impact on the supply of medication for a population. That's not a good thing to do from a health perspective, but also overall perspective. Clearly not the, I think, something that is really attractive to impose. And typically blood products have been excluded from tariffs if you look at, you know, historically at the development of tariffs. I think at this point, you know, I think way too early to actually have a real view. I don't think we have visibility in the space, and so at this point in time, I don't think there's more that we can really comment on that.

Okay, thank you. And one moment for our next question. Our next question comes from Astekas Goonwardeen of Truist. Your line is open.

Hey, good morning. Good afternoon, guys. Thanks for taking my questions. Among the centers that have treated patients in the commercial setting with their capsule, can you give us a little bit of color on what the spread is from the spread of time from site activation to getting that first patient in? And then I'll have a quick follow-up.

Yeah, so thanks for joining us, Sika. It's quite variable in terms of the time it takes to actually go from activation to actually having a patient on. For many of the centers, a lot of the activation process and the speed at which the activation process kind of went through had to do with a patient actually being suitable for the therapy and considered to be suitable for the therapy and the momentum around that. So there's some centers where there's a relatively short period in between. But you could also have situations where if the process took a certain amount of time that maybe the patient had to move on to other therapy and then there might be somewhat of a bit of a lack until the next patient might actually come along. I think the short answer is it's variable. I don't think we can easily project that within X amount of time the patients are on. We're seeing in general that the that we see centers actually get into sort of a repeat mode and actually get more than one patient obviously on, which is really good, because one of the things we'd like to see that over time, centers actually start using the product more regularly. And with that, obviously, it will start to see some element of momentum build over time. So early signs, I think, are very positive, but it's still early days.

Thanks, Christian. I know it's very early days of the launch right now, but one of the intriguing things about Alcatel was that perhaps patients do better by not being bridged to a transplant. And you've had several opportunities to talk about the data and present the data in medical journals since approval. I'm just wondering, with your initial experience right now, What seems to be the sentiment among prescribers and treating physicians? Has there been some sort of an appreciation for this, or do you think you'll still need more time and to give them more hands-on experience to feel comfortable saying, I don't want to take this patient to drug hospital? Thanks.

Yeah, I think the question with regards to, you know, is there a need for sort of subsequent therapy? You know, when we look at the trial experience, we had about 18%. the patients move to a subsequent stem cell transplant, a relatively low percentage of the patients. A lot of the patients, you know, if you had a prior transplant, actually wouldn't be eligible again for a transplant. Or they might have other, you know, comorbidities, et cetera, that would sort of prevent a transplant or make it unlikely to be successful. So it depends to some extent on the nature of the patients coming in. But overall, obviously, even in the trial, we had seen a relatively limited use of transplant. We'll need to see kind of how that develops. I don't think at this point we have, you know, we can even tell because it's just too early. But we also, based on the experiences that physicians had with the product through the development, that we would see probably initially a similar picture, and then as there's more, I think, experience gained, we need to see where that's headed. But overall, obviously very encouraging, and also an option for patients that currently you would have very limited treatment options for. And I think gives us an opportunity here to really position the product across the entire range of risk factors of age, And I think that's really where there is a significant appeal for this product because it can actually deliver positive outcomes across the entire range of the patients that we have in the relapsed refractory setting. And obviously, what we have seen is that the patients that were receiving transplant didn't appear to actually do better. And then patients who did not receive transplant and that certainly has resonated with a lot of the physicians And so we'll see how it develops I think too early to tell but overall I think a lot of conviction that There is a real opportunity for the product to be a standalone therapy without the need for subsequent consolidation And one moment for our next question

Our next question will be coming from Matthew Fitz of William Blair. Your line is open, Matthew.

Hi, Kirsten. Thanks for taking my question. I was wondering if you could just maybe comment on any of the manufacturing success rate or turnaround times so far in the commercial launch, maybe just if it's, I guess, maybe in line with some of the clinical experience. And then I assume that BioNTech has not yet made any decision on auto 6NG as far as opting in. Is there a timeline for when that might occur?

Yeah, thanks for joining, Matt. In terms of sort of the production experience that we're gaining now on the commercial side, we see that actually mirroring very nicely what the experience was during the conduct of the pivotal studies, so that's very reassuring. And obviously, you know, we're starting to get more and more experience as we're sort of running more and more products through the facility, but we're seeing a the data to track very nicely what our prior experience was. So that's the first observation. The second question was related to the options that BioNTech has. BioNTech has an option on our solitude program or the 6NG. And that's an option that actually is still running and I think is obviously going to An option, as we had indicated before, that will be triggered prior to moving the product into a pivotal study. So we're still obviously running through the current clinical study we're conducting with UCL. And so we would expect that trial to actually deliver results. And then after we have the results in and the path forward is clear, that that sort of actually would sort of be the time point for an option exercise. So it's still a little bit ahead of us here.

And one moment for our next question. Our next question will be coming from Gil Blum of Needham & Company. Your line is open.

Good afternoon, good morning, and thanks for taking our question. Just a quick couple from us. So we're going to see some of the SLE data in your upcoming R&D day. And maybe you can put that data in context. I mean, six patients. What kind of data are we going to see here? Safety, B-celioplasia, And my second question is, where would you say most of your resources as it relates to the launch are being invested? Just side rollout, or is there more to it?

Thank you. Yeah, thanks a lot. Much appreciated, Gil. So with regards to the SLE data, as I indicated, this is a cohort of six patients, those are 50 million cells. There's a set of parameters we're looking at. The first set of parameters are really understanding the properties of the product. We've seen quite a bit of variability across the various programs in terms of the ability of the products to actually expand in vivo and the sort of persistence that was observed with these products. So that's the first observation, because that gives us a sense of the quality of the product and how it actually performs. And it also gives us an ability to sort of look at and compare back to, as an example, the experience that the AeroJets team had in Erlang, which I think is still kind of the key data point or set of data points that I think the field is comparing to. So first is product property from a behavior perspective of the product itself. The second is clearly around safety. We've seen variability in terms of the safety events. So we're going to look, obviously, at the CRS. We're going to look whether there's anything that we would pick up on neurological tox. But that gives us sort of the next picture, element of the picture, in terms of the behavior of the product in these autoimmune patients. The third area is around the actual expected action of the product, and that actually goes to the depletion of B cells. So we're going to look at B cell depletion. We're also going to look at the impact on autoreactive antibodies. We're going to look at disease scores. And in particular, we're going to also look at not just the disease score as a generic score, but also to look at the individual components of the disease score, which I think is important and has certainly led to a bit of confusion during the last year when I think different data sets were compared to each other or people were trying to do that. In general, I think the patient population we're looking at is sort of a more a more real-world population that we're looking at in our Carlisle study. These are patients that do have actually significant impact on the kidney. And so it is a population that has an actual level of tissue damage that you actually do see and impact on kidney function. So it's a more real-world population compared to the very young and early in the disease population that we've seen in airline. But I think it gives us a very good view to sort of actually compare to some of those early experiences, but also gives us an understanding of the profile of the product. The follow-up obviously is limited, and that's also why we're pointing to the second half of the year for longer-term follow-up, you know, full reconstitution of the B-cell compartment post Persistence stops in those patients. So that will be sort of the second data set later in the year. But I think we're going to get a very good feel for the product and the properties that we were expected, that we expect to see in these patients. And then in terms of sort of the resources going into the launch, I think what's important about from a commercial perspective that, you know, What we're delivering with these types of therapies is really a set of services to support the centers. So it's different from your conventional commercial model, and it's much more focused on delivering services and providing support. We do that through a single point of access that actually triages and supports the center, triages the needs and requests for support. and actually is directly engaging with the centers and partners with the center very closely. I think that's sort of the model that we're running and that's obviously then supported by medical affairs as well as obviously the support on the reimbursement side and the engagement from a market access perspective. So that's sort of the distribution we have. So it's much more on the service side than it would be sort of the more classical sales and marketing functions that you would have with a conventional launch of a product. So maybe that could be helpful. Thank you.

Thank you. One moment for our next question. Our next question will be coming from Kelly Shee of Jefferies, your line is open, Kelly.

Congrats on the progress, and thank you for taking my questions. I have two. First, for the adult ARL program, curious if the first wave of treatment adoption included centers had no prior TACATAS experience, and for the centers have some hesitation to make a switch from TACATAS to what would be the top reasons you hear? Thank you.

Yeah, thanks for the questions, Kelly. I think what's been very interesting to see is that we had both centers with prior experience with OviCell as part of the Felix study, as well as centers that were not part of the Felix study that we saw actually very early on onboarding and getting activated. So it's very interesting to see that we have both types of centers actually moving very quickly. And we do see that there's clearly a substantial need there in terms of patients that were considered by those physicians to be very suitable for the treatment with OV-cell. And in their view, apparently felt that that was the appropriate treatment for these patients. So it was very interesting to see the dynamic of both types of centers to get on very quickly. And I think we're seeing, you know, very good sort of interest levels for using the product early on and across quite a wide range of patients in terms of the conditions that the patients were in. So I think overall, I think looking very positive and sort of, you know, similar to kind of the range of experience I think that we were having in the pivotal studies.

Thanks for the color. And also for SLE, you have mentioned that you could add a few more patients at a same 50 million dose or higher. Just curious, what kind of efficacy signals would drive your decision to dose higher than 50 million? Alternative question here is after several data sets, dropped from last year for cell therapy and SLE. Could you share your insights on the treatment goal of CAR-T for lupus at this moment? Thanks.

Yeah, so obviously the way we set up the study is to go in with a fixed dose, which is a translation of the pediatric ALL dose. use that as the basis for the fixed dose. That's how we arrived at the 50 million cell dose. We then had an opportunity or designed the trial in a way that would allow us to actually step up or step down. And we also have an opportunity to obviously expand the cohort. We'll provide more information obviously at the R&D day and we'll sort of give you a sense of kind of how we're moving forward and what the next steps are and where we're going to go in that space. And I think that will sort of answer, actually, I think, the question much more deeply. Fundamentally, you know, we're obviously, I think we're at a good place in terms of the experience that we had and also the safety data that we already had with the product at that dose level as well as the efficacy level and the ability to really remove B cells very, very deeply in patients based on the pediatric ALL as well as the adult ALL experience. So we think we're in a good spot there. We have a good understanding of what our product does and how it behaves. And we're looking forward to giving you the update in terms of where we're going to go next at the April 23rd R&D day. I think you had a question related to SLE and the positioning of CAR T in SLE. Did I hear that right? Yes. Okay. So I think with that I review actually in terms of the positioning of CAR Ts and SLE, I don't think has really changed. Obviously when you look at SLE in the US, you've got about 400,000 patients overall, so it's a very large population on an incidence basis. But many of these patients can be managed with standard of care at a reasonably sensible level. But you do have a small proportion of patients that do actually progress to very severe stages of the disease. where the level of intensity of therapy that we're obviously having with the CAR T therapy, we believe is very well positioned, very well warranted. And that's actually a much smaller population. We had indicated that this is somewhere between 10,000 and 20,000 patients out of the 400,000. So it's a much smaller population in the true high medical need segment of the disease where we think that this type of therapy is well suited to be used. And I think also where you have a compelling health economic argument to treat those patients with a CAR T therapy.

Thank you very much.

Thank you. We have one moment for our next question. Our next question will be coming from Yananzu of Wells Fargo. Your line is open.

Great. Thanks for taking our questions. So first, I was wondering, could you comment on, in terms of the centers onboarded, Have you onboarded the top 10 centers in terms of BALL patient volume, or is there still work to be done there? And also wondering, are you in a position to comment on number of apheresis to date, or how has that been evolving? And lastly, was wondering whether you plan to provide sales guidance at some point. And if so, when might be the right time to do so? Thank you.

Thanks a lot, Yanan. And I do understand your questions. So let me go through. First of all, have the top 10 top sensors being included. When you go onto the Elderless Assist website, you can actually see the centers that are on there. You do see that many of the top institutions in the US are already in a position to actively deliver or cancel. So I think that's something that's actually publicly visible. You see the key centers there that have very significant catchment area and very consistent high levels of patient flows. So we do believe that within those first 33 centers that we have many of the very high volume centers, there are probably only a few additional high volume centers that may not yet be active at this point. And this is why we're guiding to already within that population to cover a very substantial of providing a large portion of access to the US patients already. And that also coincides, when you look at the distribution, also with the big areas of the states with high levels of population across as well, which is another way to look at this and sort of get a feel for that. With regards to apheresis, we do not guide on apheresis. And I think there's been some companies that have tried to do that. We don't think it's going to be helpful to do that because there's obviously a time difference between apheresis collection and actually dosing of the patients, which actually then gets, I think, a very complex way of reporting and sort of following the story. So we're going to report actually on the patients that were dosed. which we think is the cleanest way of doing that because that is also the time point when, in fact, you recognize revenue. So that's important, so we're going to have a very consistent way of reporting that, and we're not going to give a leading edge sort of view based on the number of afferents. And then the last point was around sales guidance. We certainly, for this year, we will not give any sales guidance. And we don't believe that that's actually a very sensible thing for us to do, to give guidance, simply because you basically have multiple developments that you're actually going to go through that each one of them will be on a trajectory and a curve of its own. So you have obviously the number of centers that are active and you'll see that report on that and it's publicly visible. So that is also the basis to even have an ability to deliver therapy. So that momentum and the onboarding and the addition of centers obviously will sort of increase your footprint and your ability to sort of drive sales. The second aspect is that obviously within each one of the centers, there are multiple physicians that typically do deliver therapies. They have different backgrounds. And you often start with an individual physician starting to use the product. And over time and experience gain, more of the physicians we expect to start using the product. That's another kind of ramp that you're going through. And the third has a lot to do with, obviously, the experience made with the program per se. And with that, the ability to actually get access and provide access to a larger proportion of patients who today may not actually have considered access to CAR T as well. So you have several developments that each of those actually are in an individual curve. Trying to actually overlay that and project is actually very challenging and we're not planning to do that. So we're gonna actually stick with reality, which is patient's dose and revenue recognizable. And I think that gives us a very clear, very clean communication and I think will allow everybody to follow exactly where we are.

Great, great. That makes a lot of sense. If I may have a very quick follow-up on the SLE second half data update. I was wondering beyond the additional follow-up for the first six patients, what might be the incremental new data at that update? Thank you.

Yeah, so I think the most important update will be obviously the follow-up, because one of the key questions that you have with this type of a therapy is whether indeed you had a full reset of the compartment. So whether you were able to actually have an impact on the disease, remove the autoreactive antibodies, and then actually once the therapy stops working in the patient, you see the recurrence of the B cells, and what you want to see at that point is an absence of autoreactive B cells. That gives you the information that indeed you were able to do a reset in the compartment. So I think that's really important information because it gives you information about the actual clinical impact and true impact that the therapy will have. So that's the most important information. And then we're going to guide, obviously, at the April meeting and how we're going to plan going forward. But I think the primary and the most valuable piece of the information we'll be sharing will certainly be around the long-term follow-up.

Great. Thank you.

Thank you. One moment. And our next question will come in from Jacob McHale of KBC Securities. Your line is open, Jacob.

Hi there, and thanks for taking my question. I just wanted to zoom in again on the initial experience with Ocatil in the commercial setting, particularly in terms of the vein-to-vein time that you have been able to achieve. Have you been able to achieve your target of 16 days with the first few batches? And perhaps more broadly, what has been going well, and are there any learnings from the first few batches that you will implement going forward?

Yeah, so thanks for joining, Jacob. So what we see actually in doing the initial phase of the launch in terms of the turnaround time for the product is that we see a high degree of consistency with our prior experience and tracking within our expectations that we had and the guidance that we had out for the product itself. So we feel very confident that the consistency we're seeing actually builds very nicely, and we see those processes work very well. In terms of the learnings, I think one of the interesting things, of course, is that I've mentioned that in the context of the manufacturing side, it's little that patient number one coming through the door. Basically, that's when you actually turn the engine on and you start to actually have every aspect of the process from supporting the centers with information to support actually and secure reimbursement. all the way through to the actual handling of the product, the handling of the F-reset, the whole logistics chain, the manufacturing process itself, and then obviously the additional support of the center in terms of training, et cetera. So you have actually all of those items that actually start to actually run. And obviously they have to run on time, they have to be consistent, and all of the systems always have to be robust and stable. And that's an interesting transition. I think a lot of good input that we had working very closely with the centers to really focus on making sure that the experience for the centers are positive and that we're also taking as much of the workload off the centers. And I think that's been a key focus. And as you can imagine, each center works a bit differently. And so there's a lot of learnings that obviously we're going through with each one of the centers to make sure that this is as positive an experience as possible. and that we're continuously improving our platform for the engagement, the booking, and all the way through in terms of delivery of the product. So this is an ongoing process, and I think we're seeing really good collaboration with all our centers, very valuable feedback, and we're continuously looking and strive to actually improve the experience. And that's actually the process we're in. We're convinced we're going to be in that for the duration of the delivery of this product because we want to be as easy to use as possible for the centers, as easy to access as possible. And we're going to continue to work on that to make sure that that's going to be an experience that we can actually continuously improve over time. But great start, good level of engagement, great feedback, and I think puts us in a very strong position.

Okay, thank you. I just have one more, if I may, on your conversations with the EMA on the EU approval. Based on those conversations, where in the second half do you expect the approval to come? And perhaps, are you able to comment on any preparations that you're working on for the EU launch? And how does that process compare to the US in terms of center onboarding?

Yeah, so the interaction with the European agency is going through the normal process, which is very well described. And also from a timeline perspective, it's a well-defined process to go through. So that's running. We started the process in the end of March last year. So we're kind of getting to the latter part of the process. which is a series of questions, answers, additional review, final questions, again, answers, a final review, and then you go into the final steps that sort of ultimately result in an approval or no approval. So we're in that second half of the process, but I don't think it makes sense for us to actually try to pinpoint a date that wouldn't be a sensible thing for us to do because, frankly, we don't run the clock. So with regards to the preparation, I mean, very similar to what we did in the U.S. in terms of preparation, working with the clinical centers in the U.K., and we're working with clinical centers at an earlier stage in Germany as a first country that we're interested in to potentially be in a position to launch. So we're in conversation with the center who start to do the preparatory work, as we've done in the U.S. Very similar process that we're running through. And a lot of the learnings that we have made in the U.S. are very applicable also for the U.K. as well as applicable for European centers. So that's ongoing and obviously gives us a very strong basis because obviously a lot of decisions have been worked out. already for the U.S. launch, and they require typically only minimal adaptation for the jurisdictions in Europe as well. So we think we're in a very good spot there and can do that, and actually, frankly, do that work in a very efficient way.

Okay, thank you. That's very clear.

Thank you very much.

Thank you. One moment for our next question. And our last question will be coming from Simon Baker of Redburn Atlantic. Your line's open.

Thank you very much for taking my question. Two, if I may, please. Firstly, just continuing on Orcatsil and the UK. Typically, we see the importance of a NICE assessment as having relevance far beyond the borders of the UK. So just wondering if you could give us an idea on the expected timeline of a decision by NICE on Orcatsil. And then moving on to the Carlisle study. Could you give us an idea of the duration of exposure that we will see at that interim analysis for the six patients? You started dosing in February 24, so I just wanted you to give us some flavor of how much follow-up there will be across those initial six patients. Thanks so much.

Thanks, Simon. So I'll start with the second question, which is the follow-up time. Out of the six patients, we're going to have one patient with more than six months of follow-up, two patients with more than three months, and three patients that have somewhere between one and three months of follow-up. So that's sort of the nature of the follow-up, and that's also why I indicated the importance of going to the second half of the year for longer follow-up and understanding kind of the overall profile in terms of the reconstitution of the visa compartment. With regards to the UK, as you point out, there's sort of two processes that you run in the UK. You have, on the one hand, the regulatory process, which is run through the MHOA and has run through its own timeline. And then there's the second set of engagements, which is really to sort of actually demonstrate the health economic benefits of your product as part of the assessment of that ultimately will lead them to a determination of what the price in the UK is. Both processes take another insignificant amount of time, and both are processes that are ongoing, and obviously not entirely under our control in terms of the timing, but I think both are well on where they need to be relative to each other, and so we're looking forward to updating you once we're sort of actually cleared the regulatory hurdle and then obviously can talk about the final steps that you have to go through before you can actually deliver product in the UK commercially.

Great. Thanks so much. Thank you very much.

And I would now like to hand the call back to Christian for closing remarks.

Yeah, first off, thanks a lot for joining. Exciting 2024. I think we're in a really good start for 2025. We're excited about where we are with the launch, the opportunity to broaden the utility of OBSEL in the future as well. And we're looking forward to updating you at the 23rd of April at the R&D Day in New York. And obviously, we'd love to see many of you actually be able to join us in person at that event. So thank you very much, and thanks for your questions. Have a great day.

And this concludes today's conference call. Thank you for participating. You may now disconnect.