Autolus Therapeutics plc

Good day and thank you for standing by. Welcome to the Autolist fourth quarter 2025 and full year 2025 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you'll need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised today's conference is being recorded. I want to attend the conference over to your speaker today, Amanda Cray, Executive Director of Investor Relations. Please go ahead.

Thank you, Kevin. 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. On slide two, 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 OCAXL in the U.S. and U.K., auto list manufacturing sales and marketing plans for OCAXL, the market potential for OCAXL, and the status of clinical trials, development, and or regulatory timelines and market opportunities for OBSEL 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 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 Investors 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'll then take questions. With that, I'll turn it over to Christian.

Thank you, Amanda, and welcome everyone to our Q4 and full year update. As we communicated in January, we had a very good first year of launch of RazorCastle in the US with 74.3 million in revenue recognized in 2025. By the end of 2025, we had 67 centers activated and are building on positive physician feedback and reliable high quality product delivery for our second year. We are reiterating our guidance for 2026 with net revenue of 120 to 135 million. a shift to positive gross margins in 2026, and increasing our commercial footprint, targeting more than 80 activated centers by end of 2026. Regarding gross margins, larger volumes will drive down fixed costs, and improvements in the operating model will reduce variable costs per batch. By the end of 2025, we had also achieved regulatory approvals in the EU and in the UK and achieved market access in the UK, and have initiated the launch at the very beginning of this year. On slide five, alongside the launch in the US, the ROCA Consortium, which stands for Real World Outcomes Collaborative of CAR T in Adult ALL, collected data from all patients treated with Ocacil within participating institutions. Overall, 96 patients were referees, Of those, 91 actually achieved the infusions. Five patients did not receive an infusion due to medical reasons, either due to progressive disease or a combination of progressive disease and infection or a lineage switch of the disease and loss of CD19. Of the 91 patients that received the dosing, both infusions were received in all of those patients. And by the time of the analysis at the beginning of this year, 84 patients were evaluable for a day 28 assessment for response. The medium follow-up is obviously relatively short because this was the first year of launch. So the medium follow-up was 137 days from first CAR T-cell infusion. Moving to slide number six, what we're seeing in terms of the outcomes, we're looking here at both the outcome of the ROCA consortium in the real-world setting, and we actually juxtapose our prior clinical trial experience in the FELIX study. What is worthwhile realizing that the 96 patients that were actually collected in the database, approximate about 60% of the U.S. commercial patients that were treated during the course of the first year of launch. And when we look in terms of the patient population, we do see that we see a wide range of age with a median age of about 50 years, comparable to what we had in Felix and a very wide range, including patients that were very much on the elderly side already. Now, what was very encouraging was to also see that when moving to the real world setting, that we actually were able to maintain the safety profile that we have seen with a CAT cell or OB cell in the Felix study. So the real world observation was from a CRS perspective, from a cytokine release syndrome perspective, is that about 59% of the patients had a cytokine release syndrome of grade one or grade two, but no patient experienced a grade three or higher cytokine release syndrome. Similarly, when we're looking onto the ICANN site, we had 17% of the patients that experienced grade one or grade two ICANNs, and only 3% experienced grade three ICANNs in the real-world setting. When you then look at the and compare that to the Felix experience, you do see that that actually does translate very well. In Felix on CRS, a slightly higher level overall of cytokine release syndrome observed. And we also had a small proportion of 2% of the patients with high-grade cytokine release syndrome. And similarly, on the neurological toxicity side on the ICANS, we had in the Felix study 23% of the patients experiencing ICANS and about 7% experience high-grade ICANS. So overall, a very nice reproduction of our clinical experience now in the actual real-world setting. Now, when we look at the efficacy side, obviously, this is early data. So what was available is the tumor assessment at day 28. Further data may become available at later time points, but that is what so far has been analyzed and what was presented at the ASTCT meeting in an oral presentation this year in Salt Lake City. What you see is, again, on the left-hand side, the data from the real-world setting. And you can see that overall, we have about 92% overall complete remission rate in the real-world setting, which actually is quite similar to what we've seen overall from a picture perspective with the mature Felix data at three months. And it looks somewhat improved over the day 28 assessment in the Felix study. But this, again, is a very nice, I think, confirmation of the data and the observations we had in our clinical trial now in a real-world setting and in patients that were obviously now treated in the normal standard of care environment that obviously times can differ from clinical trial environments. So what is important is obviously the data is very nicely aligned with what we have prior observed, very nicely corroborating the data that we have presented in the past. But what we also do see in the patient population that there is also a wider range of patients, including from a tumor burden perspective, as you would expect in the real world setting, where once you have evidence of disease coming back, you wouldn't wait treating the patient until the patient had high disease burden, but you would intervene at an earlier time point. It's reflective of the actual standard of care that we're seeing in the disease setting. So very encouraging observation of the first year. I think for us, quite a remarkable coincidence that indeed it was the consortium was ready to collect the data practically from day one that we were able to make product available. And with that, get a real time view of the performance of the product, both from a manufacturing, from a supply perspective, but also from an outcomes perspective. So with that, I'd like to move to slide number seven. And just a brief word on the overall activities that we have in particularly around OB cell lower capsules. Obviously we have now a very strong foundation in the adult ALL segment with our first label and the product in the market and performing well in the market. And we're now obviously building on that to actually broaden the utility of the product across a range of additional indications. And obviously one of the first indications that is very natural to add is actually to aim for an ability to offer the product across the entire age range within acute leukemia. And hence, we started the work on the catalyst study, and I'll briefly show you the data in the upcoming two slides. But what we're doing with the catalyst data is really looking to actually get a data set that allows us to also get to a label for pediatric patients, We had started with a phase one data set, which was presented at ASH just at the end of last year. And based on that data and discussions with the agency, we agreed on a path to expand the study. And with that expanded study, should have the data as a pivotal study to support a future label in this particular pediatric population. The second study that obviously we've been very active in, and we also reported data on at the end of last year, first at ACR and then in an oral presentation at ASH, is the first experience that we gained in the autoimmune setting. And this is in systemic lupus with very advanced patients. It's the Carlyle study. This is a phase one study where we evaluated the activity of the product and the safety of the product in this group of patients. And we have reported initial data based on that data and also interaction with the agency. We designed then the Lumina study, which is focusing on lupus nephritis patients that are advanced patients. And we're in the process of actually enrolling that study. So that study is off the ground and running. And we expect data in 2028 for the lupus nephritis population. We have alignment with the FDA on the design and also as the design as a pivotal study to get us to enable the approval of the product if the data obviously can be generated. In addition, we're looking at progressive MS as sort of an exploratory study. That's a phase one study called the Bobcat study, which is currently enrolling. We treated the first patient in October last year. So that's enrolling and we expect to have full data for this phase one experience during the course of 2027 and hope to have early data by the end of this year to get a first view. Overall, when you look at the flow, from the pivotal study perspective, the pediatric ALL study, we expect to have data by the end of 2027. The Lumina study, again, pivotal data in 2018. And in 26 we expect obviously a longer term update and data update from the Carlisle study, which is planned for the end of the year. Now, in addition, there are additional opportunities that we see with the products that we actually have Obviously, on the one hand, a continuation of data collection that we expect to see from the RoCA consortium and sort of more of that experience being frankly collected and analyzed in their hands. And then on the other hand, there is a substantial interest for investigator-sponsored studies with a particular focus on the opportunity in frontline patients to see whether you could actually develop a definitive consolidation and have data in that space to see whether indeed there is activity in that early setting as well. So there's quite a lot of interest, obviously, to explore a broader opportunity base here for the product. And also when we look at our internal studies, I think a very nice news flow as we go through 26 and 27 into 28 with very meaningful data updates and hopefully data sets that will enable a broadening of the opportunity commercially as well for the product. With that, I would like to actually on the next two slides briefly summarize the data that was presented at the ASH conference for the pediatric experience. These are all relapsed refractory patients. And I would like to start on slide number eight with just a brief view on the safety data as it was presented at ASH. And what you can see when you go through the safety data set is you see this is consistent with what we have seen in the adult population in terms of immunological toxicity, infection risk, as well as neutropenia, which is very well characterized in this population. When we then go to slide number nine, what you can see here is a SWIM plot. First, I think to observe is that in fact, almost all patients managed to actually achieve a complete remission, either a CR or CRI. Overall, we do see that it was a CR, CRI level at the 95% level and the CR level in just around 91% of the patients. So clearly confirming the very high level of activity consistent, obviously, with what we're seeing in the adult population as well. And we start to see a good duration of responses as you sort of see the swim plot here in front of you. Obviously, the follow up is still relatively early in this population. We have a median follow up of 8.8 months. With that, I'd like to just briefly look on slide number 10 on how we're actually moving forward on the pediatric side. So we have decided to add an additional 30 patients for the phase two portion of the study. It's an international study, so we have centers in the US, UK, and in Spain active. We have developed the approach in collaboration with the Children's Oncology Group, the key group for pediatric oncology in the US. And in terms of the age range, we include patients between zero and 18 years of age. You remember that our label in the US is 18 years and older. And we have stipulated a minimum body weight of six kilogram Remember the way we dose in pediatric patients with a single infusion with one million cells per kilogram. In terms of the population that we're including, obviously these are relapsed refractory patients, and we have a particular focus on the patients that have, in the first line, a high-risk relapse. And that first-line high-risk relapse population, which is actually populations currently excluded from access to CAR T therapy, I want to make sure there's an opportunity also for those patients to benefit from CAR T therapy. And hence, we're including that population in addition to also the broader range of relapsed refractory patients. So this is where we are on the pediatric ALL side. As I mentioned, we expect to have data by the end of 2027. Moving to slide 11 and the advanced SLE population that we have studied in the Carlisle study. We have determined the recommended phase two dose in that study, which is a 50 million single infusion as the dose. When we look at the patient population that we have in the phase one, it was patients that had, to a large extent, significantly impaired kidney function, as well as quite a wide range of additional manifestations of autoimmune disease that you would actually then see represented in the SLED-I2K disease scores. And in fact, we're having overall a population with very high levels of disease scores, which obviously represent a very challenging patient population. We have now 11.4 months of follow-up in the 50 million cell dose cohort. We achieved in five out of six of those patients, a Doris response, achieved in three of six, a complete renal remission. The product was overall well-tolerated. We saw no ICANNs, and we had no high-grade CRS in these patients. And we start to get a good feel for some of the key biomarkers. And just to give you just a quick snapshot on the data, if you go to slide number 12, this is actually from the actual ASH presentation. And starting on the left-hand upper side, the summary of the safety data, obviously the key there is Overall, very good, very well tolerated the product and, you know, minimal immunological toxicity that we have picked up in the form of CRS and ICANNs. Below that, you see the SLEDI scores. You see in different colors the different manifestations of autoimmune disease. They're shown on the legend on the right-hand side of that panel. And you can see that these patients do improve over time. The blue color that you see is actually the renal scores in these patients, and obviously some of these patients already had very advanced, very challenging disease. If we go to the right upper panel, you do see kind of a depiction of the DORIS remissions, and you see that five of the six patients actually converted into a DORIS response. Adore's response actually looks at both the manifestation of the disease as you would actually have it depicted in the SLED-I score. So you need to have the SLED-I score improvement. But then you also want to see that the patients are getting down to low levels of corticosteroids of no more than five milligrams per day or less. And so it is both a measure, obviously, of the improvement overall, but also the fact that That is now a state that the patients are in where they get what's typically referred to as physiological levels of steroids. Now, at the bottom on the right-hand side, we see basically took a look at both the persistence and the recovery of the B-cell compartment. When we look at persistence, we do see that the median persistence is three months for the product. And when we look at the time to recovery, the median time to recovery for the B cells, we see that is at six months. We've seen very deep remission, a reset, a naive state after the B cells start to reappear, and then obviously over time differentiation of these cells from there on forward, but gives us clearly a deep cut and a nice sequence of loss of persistence, followed by recurrence of B cells, as you would expect from a mechanism of action perspective. When we then go to slide 13, this is a quick look at the way that we are developing in lupus nephritis. We've obviously done the Carlisle study. We selected the dose. We actually also have included now in the Carlisle study and report at the end of the year also teenagers, patients 12 years and older, and include that population as well, because we believe it's a particular medical need and quite often a very aggressive course of the disease in these teenagers and young adults. Based on this data, we're moving or have moved into the LUMINA study, which is a single-arm 30-patient study in patients that have gone through B-cell depleting antibodies and calcineurin inhibitors. failed on both and are now basically outside the approved standard of care for that stage of the disease. The study is enrolling and we're actually active in the US and the UK, in Spain, and we're likely going to add one or two additional countries on top. When we then think forward, obviously there is an opportunity once you actually create a foothold in the indication to then think about the ability to broadening the use of the product in a wider set of patients. And that's going to be sort of the second step once we sort of achieved our first approval in the indication. We expect data for the Lumina study as indicated in 2028. And then finally on slide 14, just as a reminder, the progressive MS study that we're conducting in the Bobcat study, And obviously here, really what we're looking at is both the safety or the safety profile on the one hand, the clinical impact from a disease score perspective, as well as a range of biomarkers and imaging measures to understand the activity of the product in these patients. And obviously, depending on outcome, we'll move from there. So with that, we're getting to the financial results section, and I'm handing over to Rob.

Thanks, Christian. And good morning or good afternoon to everyone. It's my pleasure to review our financial results for the fourth quarter of 2025. And I'll be referring to the information on slide 16. Before diving into the specific numbers, I would like to note a refinement to the accounting treatment related to our product revenue and cost of goods sold that are reflected in the results that we'll discuss today. Importantly, this change has no material impact on our existing or anticipated Alcatel revenue and has a practical benefit of better aligning the timing of revenue and cost of sales. On a full year 2025 basis and moving forward, we plan to recognize both the full value of product sales and the associated cost of goods sold upon confirmation of the second dose administration for Alcatel. From a revenue perspective, this means we will no longer recognize a 50-50 split across the first and second dose confirmation. This also eliminates the previous deferred revenue accounting and earlier cost of goods recognition associated with those deferred revenues. The accounting for personalized cell therapy products is an emerging area And during our year-end reporting review process, we and our auditor concluded on this refined position within the accounting standards, and again, with no material impact on the financial statements. Now onto the results. Net product revenue for the fourth quarter of 2025 was $23.3 million, bringing us to a total of $74.3 million for the first full year of Alcatel sales. I'll also note that we also recorded a $1 million license revenue component in Q4 2025 related to the achievement of a clinical milestone under our license and option agreement with Moderna. Combined, this gives you the $24.3 million in total revenue for the fourth quarter. Cost of sales in the fourth quarter totaled $25.3 million, and that's compared to $11.4 million for the same period in 2024. This change was primarily driven by having a full quarter of sales in 2025 and having only a partial quarter of commercial manufacturing activity expense recognition upon FDA approval back in November of 2024. Additionally, cost of sales in Q4 2025 includes canceled orders in the period, patient access program product, inventory reserves or write-offs, third-party royalties for certain technology licenses. As discussed on our full year guidance, we expect to shift to positive gross margin this year based on increasing patient volume, improving overall plant utilization, together with executing on operational efficiencies. Moving on, our research and development expense was $35.6 million for the fourth quarter of 2025. That compared to $30.8 million during the same period in 2024. This change was primarily driven by an increase in research and development activities, including some of our new clinical trial startup and a reduction in the period over period UK R&D tax credit. This was partially offset by commercial manufacturing related employee and infrastructure costs that have now shifted to cost of sales and inventory. Our selling, general, and administrative expenses increased to $35.8 million for the fourth quarter of 2025, compared to $33.7 million in the same period in 2024. This increase was primarily due to salaries and other employee-related costs driven by the increased headcount supporting the commercialization activities. Our loss from operations for the three months ending December 31, 2025, was $72.5 million as compared to $75.9 million for the same period in 24. And finally, net loss was $90.3 million for the three months ending December 31st, 2025 compared to $27.6 million for the same period in 24. Our cash, cash equivalents, and marketable securities at December 31st, 2025 totaled $300.7 million

Hello, Rob. Rob, are you still there?

Pardon me, Amanda, can you hear me?

This is Christian. I can hear you.

Okay. Looks like we might have just lost Rob.

Okay. I think I'm going to take over. Are you back now? Sorry about that. Are you back? Okay.

Okay, I'm going to pick up on our cash and cash equivalents and marketable securities. At the end of 25, totaled $300.7 million as compared to $588 million at the end of December 2024. That decrease was primarily driven by net cash use and operating activities and impacted by a delayed receipt of approximately $18.6 million related to the 2023 R&D Tax Credit that we are expecting from the UK HMRC. As Christian noted, we are reiterating financial guidance issued in January that we expect between 120 and 135 million in El Paso net product revenue in 2026. This includes contribution from both the US and UK markets. Finally, based on our current operating plans, including anticipated El Paso net revenues, we expect that current and projected cash equivalents in marketable securities will be sufficient to fund our operations into Q4 2027. I'll now hand back to Christian to wrap up with a brief outlook on expected milestones. Christian.

Thanks Rob. All right, so going to slide 18, upcoming milestones. We're actually just about two weeks away from a virtual KOL event that will be focused on acute leukemia and the opportunity there. I'll talk a little bit more on the next slide about that. We then actually have, if you look into 26, we expect towards the end of the year, longer term follow up from the Carlisle phase one trial. We also expect first data from our AutoAid program in collaboration with UCL on light chain amyloidosis. Name of the trial is Alaric. And early data from the Bobcat phase one trial in progressive MS. The full data for Bobcat is then expecting during the course of 2027. And we also, by the year end of 27, expect the full phase two data for the catalyst study, which is designed as a pivotal study. And then the second pivotal study, the Lumina study in lupus nephritis, is expected to read out in 2028. So with that, just a quick look on slide 19, the event that we're planning for April 8. We got a great group of speakers who will talk through the landscape and the opportunity. It starts with Dr. Jay Park from Immortal Sloan Kettering, who will talk about the adult ALL treatment landscape and unmet medical need. Dr. Laurie Muffley from Stanford will talk through the RoCA real-world experience with the council. Dr. Elias Jabour from MD Anderson will look at the opportunity in the earlier lines of treatment in ALL and particularly through the lens of investigator sponsored trials. And then we will get to the pediatric population with Dr. Michael Pulsifer from Utah University Huntsman, who will look at the medical need in the pediatric patients and the initial data that we have from the catalyst study. The event obviously is gonna be webcast and also will be recorded. And also we're looking forward to hopefully many of you being able to join us. A great group of speakers and I think a very nice direct feedback and sense for where the disease setting is and where the opportunities are and also obviously their perception of how a capsule fits into this landscape. With that, just to finish and to wrap up, the focus for 2026, clearly drive market share for a capsule. improve the gross margins for the product, and expand the utility of OB-Cell with the clinical trial programs, development programs that we have ongoing that are designed to give us overall a broader range of indications ultimately to be able to serve with OB-Cell. With that, I think we're at the end of the prepared remarks, and we're happy to take questions.

Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star 1 1 on your telephone. If your question has been answered, you wish to move yourself from the queue, please press star 1 1 again. We will pause for a moment while we compile our Q&A roster.

Our first question comes from James Shin with Deutsche Bank. Your line is open.

Hey, good morning, guys. Thank you for the questions. I have a couple. For the 2026 guide of 120 to 135 million, Christian, can you, or Rob, can you guys help us with how much might come from UK and other XUS regions? Secondly, what's the latest on more EU adoption or reimbursement for OCATL? And then Christian, given we're pretty much through 1Q26, can you shed any light on how OCATL update has trended? Thank you.

Yeah, well, first of all, thanks a lot for joining James. So with regards to the UK guidance, as Rob said, this includes both the US as well as the UK. We're not planning to break that out. Obviously, we're early on in the launch. The UK is a substantially smaller country. than the US and much more the population. So we're going to be actually presenting the data in the aggregate. We do not expect a major contribution yet from the UK, given that this is obviously very early in the process. So at this point, I think too early to tell and probably too early and frankly too early to break out. With regards to other EU countries, we do not expect in 2026 any contributions from EU countries. As you remember, we have an approval in the EU and we're actually in conversation with market access authorities in Europe to see whether there's appropriate paths here for us to take. I think what is very clear for us is that obviously we need to be able to enter a market in a way that actually is economically sensible and different from maybe some of the larger players, we cannot afford actually taking a loss doing that. So we're in the process of evaluating and we certainly will keep you updated as we learn more and we get a better understanding of the dynamics here. But for 2026, we're not actually guiding to any revenue coming outside of the US and UK. And with regards to Q1, obviously we're not going to break out individual quarters. We've given you the full year guidance as we had actually at the beginning of the year and now reiterate it. I think in overall, when you look at during the course of last year, what we certainly saw were elements of seasonality that were picking up and certainly as you sort of go through in the summer with vacation periods that are clearly visible. as well as kind of the year-end holidays, do have an impact on patients, particularly those patients that have an ability to, frankly, buy some time or bridge some time and obviously are interested to sort of spend time with their families, particularly over Christmas and New Year's. So there's elements there that we'll see over the years, but overall, we're not going to give, I think, any sort of particular guidance per quarter because, frankly, there's too much variability in those numbers, but we're confident on the aggregate for the full year.

Thank you. One moment for our next question. Our next question comes from Gil Blum with Neededman Company.

Your line is open.

Good morning and good afternoon, and thanks for taking our question. So, very nice rocker results. Do you think this is going to influence physician behavior? Is this sufficiently socialized? Feedback that we've gotten is that most physicians already view OCATL as a preferred therapeutic.

Thanks for joining, Gil. Obviously, we're very pleased with the observation, the real-world observation. And I think what's important to understand in this disease setting is that, obviously, this is an incidence-driven disease. It's a one-time therapy. And so what's really at the core of your ability to actually build market share is the continued buildup of confidence, experience, and confidence that the treating physicians have. So that's a critical component in that, obviously, the ROCA data, which is the physician's own data, obviously is very important. Now, we have to understand when we look into kind of the physician groups that actually are treating ALL patients, This is not just the transplanters or CAR-T therapists that actually are treating ALL patients, but a wide range of hematontologists who are treating them, and particularly in the frontline and early relapse setting. So there's a lot of work that we do to sort of expand, obviously, the adoption of the product across the range of stem cell transplanters and CAR-T therapists, but also increase the awareness within the group of those physicians that tend to do the frontline therapy. So those are kind of the key dimensions that we're working on. And obviously, the data is very important because this is their own data, their own experience in many of the centers, or for many of the centers that are very relevant for the treatment of ALL patients. So we think the data is very important, but there is a you know, substantial amount of work that we have ahead of us to sort of go from a market penetration that is probably somewhere around the 10% range to really start driving that towards the levels of penetration that we're seeing with Blindsighter, which is what we believe actually the actual potential would look like.

Thank you for that. And are there any insights you can provide on how the Lumina enrollment is going?

So the Lumina study, as I indicated, is taking place in several countries. We started out in the UK and obviously building on the initial experience from the Carlisle study. So that is starting to get, I think, to start to gain good momentum. We're in the process of adding US centers, and we expect US centers to come online in the upcoming quarter. And with that, I think we're going to start to see, I think, a very nice sort of development in the disease setting and in the enrollment characteristics. So far, we're seeing kind of what we had expected to see in the indication and then seeing the type of flow of patients consistent with what our expectations were.

All right. And one last one for Rob. So now that we're recognizing revenues and costs on the second dose, How should we view patients who only receive one dose?

Yeah, thanks for the question, Gil. Maybe just as a reminder on that, I mean, if you go back to the experience in the clinical study or even commercial experience last year, we're talking about a relatively small number of situations in patients. So they don't get the second dose. So the cutoff will be certainly if there's a first dose towards the end of a quarter, that patient may still get the second dose. That revenue won't be recognized. But if they get the second dose in the next period, it would be recognized then. If the patient only ever gets the first dose, that's going to be a situation where there's a number of factors that will feed in. depending on the type of patient in terms of the split CMS reimbursement or credits according to the trade policy that may apply. But eventually what will happen there is we will wait until cash receipt to recognize that revenue on that individual patient. Whether it's a full reimbursement or a 50% reimbursement, it really depends on the patient characteristics. Gotcha.

Thank you, and congrats on the progress.

Thanks a lot, Gil.

One moment for our next question. Our next question comes from Salem Said with Mizuho. Your line is open.

Great. Thanks for the question, guys, and congrats on the progress. There's one for us on cadence of catalysts for this year. So I know we're getting a lot of data here at the year end of 26, but a lot of these trials, like Bobcat, Lumina, et cetera, I think even Aleric, are all open label studies with, you know, I presume you're going to be looking at data through the course of the year. Is there any potential here? on these studies for potential early disclosure? And can you just remind us specifically in Bobcat the intervals that you'll be measuring disability progression? Thank you.

Yeah, really good question. Thanks for joining us. With regards to catalysts, on the Carlisle study, obviously, we have presented the baseline data at the end of last year. So what the next real question for that study is really kind of the longer term outcome in these patients and obviously also the additional experience in the adolescent patients. We don't think we're going to make sense to actually to piecemeal that data. I think you want to give a proper update with a comprehensive review of the data, which is what we're planning to do. With regards to the alaric study, so that's the first data cut we're going to do in that study. Obviously, you want to have enough patients and also from a dose level perspective, have enough experience to actually look at the data and understand kind of what the impact of the treatment is. With regards to Bobcat, one of the key things that obviously you'd like to understand is on the one hand, the pharmacodynamic markers that you can look at and some of the imaging markers. But you also want to obviously see whether there is actually any sign of clinical activity eventually, and that will actually take time to build. So in a way it's tempting to look very early, but the thing is you will not actually have any understanding whether or not there is a clinical, anything you could link to a clinical outcome And I think ultimately, that's ultimately what we would like to do is to be able to sort of make these connections. But even if you look at the pharmacodynamic markers, you need a certain number of data points that you collect so you understand what trends are to actually get a good sense of what it is you're looking at. The individual data points, I think, are tricky, particularly early on and can be misleading. we're not planning to actually come early with with data from Bobcat. That doesn't make sense because I think the data probably will be not interpretable as much as we can get excited about individual patients and individual observations. So we're planning to come towards the year end, but we're not expecting to come earlier than that. Cause I don't think it's helpful.

Okay. Thanks. And same on, same on lumen. I presume there'd be no potential early disclosure here when that's open label.

Well, it's open-label, but it's also a pivotal study. So the thing you don't want to do is you don't want to actually start to put information out that may actually impact the trial itself. And that's particularly tricky in single-arm studies and open-label studies. So that's something you absolutely would not do. And remember, we didn't do that with the Felix study either, because you start to risk actually the integrity of the study.

Okay, super helpful.

Thanks so much, Christian.

Thanks, Liam.

One moment for our next question. Our next question comes from Matt Phipps with William Blair. Your line is open.

Thanks for taking my question. I'm a progressive MS student. study. We're kind of hitting on this, but just, I guess, follow up. Stanford recently presented data on six patients at Actrims. And, you know, a couple of patients maybe saw some improvements by six months in EDS scores and CSF oligoclonal bands. Do you have any thoughts on this data and how, you know, that makes you think about what you could present in Bobcat later this year? And then for AutoAid and ALM and DOSIS, similarly, I mean, Siltacel has shown very high response rates. in that setting, what do you think the CD19 aspect of AutoAID gets you as far as differentiation from Silvacel? Thank you.

Yeah, very good questions. Thanks, Matt. So with regards to the data that was presented at ECTRIMS from the Stanford team, I think overall encouraging data, they're showing certain correlations between pharmacodynamic markers, and there's early observations on the the disease score in these patients. The challenge, and this goes back to the answer I gave to Salim before, the challenge is that also part of those disease scores also include patient assessment and physician assessments, which obviously can be more subjective. And that actually creates some of the challenges in the interpretability of that data, particularly if you look at it early on. Overall, what you'd like to see is probably some congruence between pharmacodynamic activity and some early indication of activity. And we think that stage we're probably going to reach sometime next year in 27 with a longer-term follow-up and more stability in the data. I think early on, you'd be looking more at some of the pharmacodynamic markers and general presence and product properties. persistence, you know, presence of the product in CSS, those types of assessments that you'd be looking at. And then obviously, you know, B-cell depletion data and so on. But I think in terms of going from there forward and sort of concluding whether or not you might actually have the type of clinical outcome, I think will be premature in the early time points. I think we get a better sense for that during the course of next year, but it takes a longer observation time to start to be able to have put some weight on that. What was encouraging with the Stanford data was it suggested that the patients did improve, but again, it's early data and it's early days, but definitely worthwhile, obviously, pursuing and, frankly, figuring it out. And then with regards to the alaric data, so that's obviously light chain amyloidosis, predominantly a plasma cell disorder. And what we're looking at there is we're actually looking predominantly at the action of the BCMA component of the product. And then we're going to see whether or not the CD19 component adds to that or not. But the fundamental activity we expect, obviously, very clearly to be driven by the BCMA, either predominantly or maybe even exclusively.

Thank you. One moment for our next question.

Our next question comes from Roger Song with Jefferies. Your line is open.

Hi, this is Fiona for Roger. Congrats on the quarter, and thanks for taking our question. So understand that you will shift to a positive gross margin this year, and how should we think about the near-term involvement of gross margin once it turns positive? And with your partnership with Solaris, early this year, how quickly can this automated platform be integrated into your commercial supply chain? And what's the magnitude of cost reduction do you expect from this approach?

Thanks. Yeah, very good questions. Thank you. So let me start out with just what we're doing in order to actually drive down overall production costs and also with that improve gross margins for the product. The two key areas, one is quite obvious, which is you run more products through the infrastructure. And with that, the fixed cost obviously can be broken down to a large number, a larger number of products. And with that, the contribution of fixed costs becomes reduced on a product per product basis. That's very straightforward. The second aspect, which is really critical, though, is that we're also doing a lot of work in optimizing the operating model that we have in our facility and really are optimizing every step along the way. And between those two elements, the optimization on the one hand and the higher level of volume through the facility, we actually can drive the cost down substantially over time. Overall, that is going to be the key trajectory we're going to be on and will be the key driver to get us to an economically attractive place. The Solaris opportunity is obviously one where we do a feasibility study to see what the comparability of the data between the two different manufacturing setups, which are just, you know, from an operating setup slightly different, but obviously the biology that you're running is the same biology in the two systems. For us, the particular interest is actually for situations where we might actually have to scale substantially because of a new indication that we might be able to unlock that may require us to actually set up a substantially larger manufacturing capacity. And so when we look at Solaris, this is much more an ability to scale to a substantially higher level of volume rather than actually to drive down costs. The primary focus is actually on the ability to scale. And the reason why we're looking into it is that we obviously do not know where we're gonna come out on some of the new indications, particularly also on MS, but assume a positive outcome in MS. That could actually drive substantial demand and substantial need to be able to stand up capacity And that is sort of the context under which we're actually looking at this and we're looking at doing the feasibility work because we believe that could be an attractive way to actually scale and scale in an economical way. It doesn't actually take anything away from what we're doing at our own facility, at the Nucleus facility, which is obviously really focused on delivering for the ALL patients and the smaller subsets of the autoimmune patients, which is what the facility is designed to support.

Very helpful. Thanks, Christian.

Thank you.

One moment for our next question. Our next question comes from with Wells Fargo. Your line is open.

Oh, great. Thanks for taking our questions. Just maybe a follow up to the primary MS study questions earlier. The study has three dose cohorts. At the year end readout, can you talk about how many dose cohorts could we expect and whether a signal of efficacy can be discerned from a kind of dose response on some of the metrics? And if you could, you know, be A little more specific on BAR for success, that would be very helpful. And I have a follow-up as well. Thank you.

Okay. Thanks for joining, Yiran, and all really good questions. Obviously, this is an exploratory study, which means that we expect this is a study where we will actually learn quite a bit along the way. We've designed it as a dose escalation study. What we do know is that the product obviously does give us an ability to penetrate the brain barrier and be active in the brain. We've seen that with acute leukemia patients with CNS involvement. We've seen it also in primary CNS lymphoma patients. So we know the product has the right properties. It has an ability to do that. What the appropriate dose level is, is something we're evaluating in this study. We started at 100 million cell dose. We have an ability to either step up or step down. Both is possible. And obviously, one of the key things we're going to be looking at is the presence of CAR T cells in CSF as a measure of the ability to actually cross the blood-brain barrier. and going to the compartment that we know that the systemically applied therapeutics typically cannot actually get to and typically cannot be active in. So that's where the mechanism helps a lot and gives us sort of a differentiation here. Now, in terms of what we're sort of working through is obviously working through the dose levels. We need to have with each one, I think, a reasonable level of follow-up. So by the end of the year, I think it would be really very early data from our initial dose cohort to get a feel for what that data might look like. And it'll be, as I indicated, predominantly around the product properties in terms of expansion, safety profile, obviously, the ability to sort of actually access the CSF. And then I think additional sort of typical pharmacodynamic markers, including B-cell depletion and so on. And then we're going to obviously record all the typical other parameters that you can record both biochemicals imaging parameters. And we'll see whether there's any correlation between any of these parameters. I think it will be very, it will be too early to actually understand where there are true connections and where there's a link to outcome. I think that is just not enough observation time. But we believe as we go through the course of next year that we start to get to a place where we actually have a longer observation time with that, have an opportunity to start looking more at clinical impact and hopefully can put more emphasis, but also more trust in the data that we're collecting on the clinical side. just given the inherent variability that that data can actually represent. So that's where we are. So it'll be an early peak, but then the much more relevant data during the course of 2027.

Great. Thank you. That's super helpful. Then on the BALL launch for Arkansas, can you comment on whether there's any use in earlier line setting, such as MRD positive consolidation. And also we see there is a Sloan Kettering ITT that just opened for MRD negative consolidation. Can you share your thoughts on how that could be leveraged in expanding the opportunity? Thank you.

Right. So in terms of the actual use, current use, what we're seeing is that, and this was what was presented at the ASTCT meeting, and Laurie will talk more specifically to it, but what we're seeing is, similar to what we've seen with other products in the relapsed refractory setting, that patients can be included that actually have mineral residual disease or low disease burden at the time of inclusion. They're still relapsed refractory, so it's the same setting, but it's basically inclusion at a time when the disease hasn't actually grown quite to the level of morphological disease. So that we do see in the data. We see maybe about a third of the patients, give or take, in that bucket. which is frankly what you would expect to see. This is the standard of care. This is the way these patients are being assessed. And the intervention is done when you see, when you have evidence of relapse. And as I mentioned, none of the physicians will wait for things to get worse for a patient when they already have evidence of the disease coming back. So we do see that, which is very expected in terms of the real world setting. I don't think we have patients that actually are in a frontline MRD setting at this point. I don't think we do. But that's something that we'll need to sort of look at and sort of see more kind of data coming back from the consortium to see whether indeed that might happen over time. It's not something that we expect to see for the time being. Now, what you've picked up with the memorial entry in clinicaltrial.gov is a trial that's done in connection with other centers across the U.S., and there's a second study as well in the U.S. that they're currently looking for as an investigator-sponsored studies where those investigators are interested in exploring the use of Obicel in frontline patients that have gone through the initial frontline treatment And then actually have either evidence or no evidence of disease in the studies where it differ in terms of their designs in that regard. To then do with consolidation, but do in essence have an ability and look at a population or to patients that were treated not for the full extent of frontline treatment, which is like an 18 months treatment with quite a range of therapeutics. And then at the end, put the CAR T, but rather actually look at an abbreviated initial therapy and aim for a definitive consolidation. That's the thought process that these investigators have sort of brought forward and what they're interested in looking at. And also it's an area we're very interested in. And from a fundamental perspective, certainly if you think about it from a patient perspective, it would be desirable to find therapies that actually can actually reduce the overall treatment time and reduce the overall amount of toxicity that the patients do get exposed, particularly in the frontline treatments. So we understand that there could be real benefit in those settings, and I think we'll learn from those investigators' experience, and we'll get a sense for the profile of the product in those patients.

Great. Thanks for all the cover.

Thank you very much, Janen. One moment for our next question. Our next question comes from Emily Budnard with HC Wainwright. Your line is open.

Hi, good morning. Thanks for taking the question. I guess, how much additional follow-up and durability data should we expect from the Carlisle trial later this year for those 50 million and 100 million cell doses? And what are you kind of looking to see to gain additional confidence in the Lumina trial? Thank you.

Yeah, thanks a lot for joining, Emily. So the Carlisle study, I did mention we had 8.8 months of follow-up for the data cut at ASH. I would assume for that, and that's the initial cohort of the 50 million cohort, I would assume we have 12 more months, between six and 12 more months, depending on when the exact data cut happens. So we're looking at somewhere in the range of one and a half years to close to, well, probably around one and a half years of follow-up for the 50 million cohort. And the 100 million cohort will probably be just under probably a year of follow-up at that point in time, and probably half a year follow-up for the adolescent patients. So that's kind of the ballpark in terms of follow-up that we expect. And in terms of the luminous study, the difference with the luminous study is that the population is slightly different. In the Carlisle study, it was SLE patients with organ involvement. Happens to be that the vast majority of these SLE patients had pretty significant kidney damage and kidney involvement. So they had a lupus nephritis component to their disease. What we're having here in the Lumina study is more precisely defined the population, and it's defined by the prior lines of treatment that the patients went through. In this case, in the Lumina case, it's a CD20 or other B-cell depleting antibodies and calcium urine inhibitors being after those two lines. And at that point in time, you actually get to the outside the approved therapeutics from a label perspective. And so it's more defined, it's more defined population. And then there's obviously a range of kidney, level of kidney damage and a requirement for the inflammatory process to be ongoing. So then this type of an approach has an ability to improve the outcome. So it's a different definition of the patient's. Obviously, very similar overall properties, but it's a different way of defining the patient population as the basis to then actually have a definable primary endpoint that would be interpretable from a pivotal perspective.

Thank you.

Thanks, Emily. Ladies and gentlemen, we've reached the conclusion of the Q&A portion of today's conference. I'd like to turn the call back to Christian for any further remarks.

Well, first of all, thanks everybody for joining. We're looking forward to hopefully seeing or hearing from most of you on April 8th when we have the KOLs talk to us about the ALL disease setting and the opportunities. And obviously after that, it's not far out and we're going to be meeting again for the Q1. So thank you very much for joining today and wish you all a good time.

Thank you, ladies and gentlemen. So that concludes today's presentation. We thank you for your participation. You may now disconnect and have a wonderful day.