Autolus Therapeutics plc (AUTL) Q4 2025 Earnings Report, Transcript and Summary

Good day, and thank you for standing by. Welcome to the Autolus Fourth Quarter 2025 and Full Year 2025 Financial Results Conference Call. [Operator Instructions] Please be advised today's conference is being recorded. I would now like to hand 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 are Chief Executive Officer, Dr. Christian Itin; and Chief Financial Officer, Rob Dolski. On Slide 2, 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 AUCATZYL in the U.S. and U.K., Autolus manufacturing, sales and marketing plans for AUCATZYL, the market potential for AUCATZYL and the status of clinical trials, development and/or regulatory time lines and market opportunities for obe-cel 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 Investors section of our website. On Slide 3, 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 have communicated in January, we had a very good first year of launch with AUCATZYL in the U.S. 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 million 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 cost per batch. By the end of 2025, we had also achieved regulatory approvals in the EU and in the U.K. and achieved market access in the U.K. and have initiated the launch at the very beginning of this year. On Slide 5, alongside the launch in the U.S., the ROCCA Consortium, which stands for real-world outcomes collaborative of CAR T in Adult ALL, collected data from all patients treated with AUCATZYL within participating institutions. Overall, 96 patients were apheresed. Of those, 91 actually achieved the infusions. And 5 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 median follow-up is obviously relatively short because this was the first year of launch. So the median follow-up was 137 days from first CAR T cell infusion. Moving to Slide #6. What we're seeing in terms of the outcomes, we're looking here at both the outcome of the ROCCA 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. 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 AUCATZYL or obe-cel 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 1 or Grade 2, but no patient experienced a Grade 3 or higher cytokine release syndrome. Similarly, when we're looking in the -- on to the ICANS side, we had 17% of the patients that experienced Grade 1 or Grade 2 ICANS and only 3% experienced Grade 3 ICANS in this -- 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. We had 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% experienced 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 the -- 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 ASGCT 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 3 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 at 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 included 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 1 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 #7. And just a brief word on the overall activities that we have, in particularly around obe-cel oral capsule. 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 natural -- it's 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 CATULUS study, and I'll briefly show you the data in the upcoming 2 slides. But what we're doing with the CATULUS 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 1 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 CARLYSLE study. This is a Phase 1 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 1 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 1 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 '28. And in '26, we expect, obviously, a longer-term update and data update from the CARLYSLE 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 ROCCA 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 -- from that -- 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 2 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 #8 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 #9, 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 #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 2 portion of the study. It's an international study. So we have centers in the U.S., U.K. 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 U.S. And in terms of the age range, we include patients between 0 and 18 years of age. You remember that our label in the U.S. is 18 years and older. And we have stipulated a minimum body weight, to 6 kilogram. Remember, the way we dose in pediatric patients with a single infusion with 1 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 -- sorry, 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 obviously 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 CARLYSLE study. We have determined the recommended Phase 2 dose in that study, which is a 50 million single infusion after the dose. When we look at the patient population that we have in the Phase 1, it was patients that had to the 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 SLEDAI-2K disease scores. And in fact, we're having overall a population with very high levels of disease scores, which obviously represent a very challenging to patient population. We have now 11.4 months of follow-up in the 50 million cell dose cohort. We achieved in 5 out of 6 of those patients, a DORIS response, achieved in 3 of 6 a complete renal remission. The product was overall well tolerated. We saw no ICANS 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 #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 product and minimal immunological toxicity that we have picked up in the form of CRS and ICANS. Below that, you see the SLEDAI scores. You see in different colors, the different manifestations of autoimmune disease that are 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 5 of the 6 patients actually converted into a DORIS response. The DORIS response actually looks at both the manifestation of the disease as you would actually have it depicted in the SLEDI score. So you need to have the SLEDI score improvement. But you also want to see that the patients are getting down to low levels of corticosteroids of no more than 5 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 3 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 6 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 this is 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 CARLYSLE study. We selected the dose. We actually also have included now in the CARLYSLE 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-patients 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 in this -- for that stage of the disease. The study is enrolling, and we're actually are active in the U.S., in the U.K., in Spain, and we're likely going to add 1 or 2 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 obviously, 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 AUCATZYL 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 AUCATZYL. From a revenue perspective, this means we will no longer recognize a 50-50 split across the first and second dose confirmations. 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 reported 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 on to 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 AUCATZYL 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 start-up and a reduction in the period-over-period U.K. 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 3 months ended 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 3 months ending December 31, 2025, compared to $27.6 million for the same period in '24. Our cash, cash equivalents and marketable securities at December 31, 2025, totaled $300.7 million.

Hello, Rob? Rob are you still there? SP1 Pardon me, Amanda, can you hear me?

This is Christian. I can hear you.

Okay. Looks like we might have just lost Rob. . [Technical Difficulty].

Okay. I think I'm going to take over.

Sorry about that.

Are you back? Okay.

Okay. I'm going to pick up on the -- 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 used in 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 U.K. HMRC. As Christian noted, we are reiterating financial guidance issued in January that we expect between $120 million and $135 million in AUCATZYL net product revenue in 2026. This includes contribution from both the U.S. and U.K. markets. Finally, based on our current operating plans, including anticipated AUCATZYL net revenues, we expect that current and projected cash, cash equivalents and 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 2 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 CARLYSLE Phase 1 trial. We also expect first data from our AUTO8 program in collaboration with UCL on light chain amyloidosis. Name of the trial is ALARIC and early data from the BOBCAT Phase 1 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 2 data for the CATULUS study, which obviously 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. Jae Park from Memorial Sloan Kettering, who will talk about the Adult ALL treatment landscape and unmet medical need. Dr. Lori Muffly from Stanford will talk through the ROCCA real world experience with AUCATZYL. Dr. Elias Jabbour 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 Pulsipher from Utah University Huntsman, who will look at the medical need in the pediatric patients and the initial data that we have from the CATULUS study. The event, obviously, is going to be webcast and also will be recorded. And 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 AUCATZYL fits into this landscape. With that, just to finish and to wrap up, the focus for 2026, clearly drive market share for a AUCATZYL, improve the gross margins for the product and expand the utility of obe-cel 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 obe-cel. With that, I think we're at the end of the prepared remarks, and we're happy to take questions.

[Operator Instructions] Our first question comes from James Shin with Deutsche Bank.

I have a couple. For the 2026 guide of $120 million to $135 million, Christian, can you -- or Rob, can you guys help us with how much might come from U.K. and other ex-U.S. regions? Secondly, what's the latest on more EU adoption or reimbursement for AUCATZYL? And then Christian, given we're pretty much through 1Q '26, can you shed any light on how AUCATZYL uptake has trended?

Yes. Well, first of all, thanks a lot for joining, James. So with regards to the U.K. guidance, as Rob said, this includes both the U.S. as well as the U.K. We're not planning to break that out. Obviously, we're early on in the launch. The U.K. is a substantially smaller country than the U.S. and much smaller population. So we're going to be actually presenting the data in the aggregate. And we do not expect a major contribution yet from the U.K. 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 other -- 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 path 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 are not actually guiding to any revenue coming outside of the U.S. and U.K. 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 reiterated. I think in overall, when you look during the course of last year, what we certainly saw were elements of seasonality that we're picking up. And certainly, in the -- as you sort of go through in the summer with vacation periods that is clearly visible as well as kind of the year-end holidays do have an impact on patients, particularly those patients that are -- 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, New Year's. So there's elements there that we 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.

Our next question comes from Gil Blum with Needham & Company.

So very nice ROCCA results. Do you think this is going to influence physician behavior? Is this sufficiently socialized? I mean feedback that we've gotten is most physicians already view AUCATZYL 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 onetime 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 ROCCA 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 the wide range of hemato-oncologists 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 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 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 Blincyto, which is what we believe actually the actual potential would look like.

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 U.K. and obviously building on the initial experience from the CARLYSLE study. So that is starting to get -- I think, to start to gain good momentum. We're in the process of adding U.S. centers, and we expect U.S. 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 only receive one dose?

Yes. Thanks for the question, Gil. So 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 second -- in the next period 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.

Our next question comes from Salim Syed with Mizuho.

Congrats on the progress. Just 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 ALARIC are all open-label studies with -- 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 on BOBCAT, the intervals that you'll be measuring disability progression?

Yes. Really good question. Thanks for joining us. With regards to CATULUS the -- on the CARLYSLE study, obviously, we have presented sort of 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. So we're not planning to actually come early with data from BOBCAT that doesn't make sense because I think the data probably would 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 because I don't think it's helpful.

Okay. And same on LUMINA, I presume there'd be no potential early disclosure here 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 -- we didn't do that with the FELIX study either. Because you start to risk actually the integrity of the study.

Our next question comes from Matt Phipps with William Blair.

On the progressive MS study, you were kind of hitting on this, but just, I guess, a follow-up. Stanford recently presented data on 6 patients at ACTRIMS. And a couple of patients maybe saw some improvements by 6 months in ES scores and CSF oligoclonal bands. I guess any thoughts on this data and then how that makes you think about what you could present at BOBCAT later this year? And then for AUTO8 and AL amyloidosis, similarly, I mean, cilta-cel has shown very high response rates in that setting. What do you think the CD19 aspect of AUTO8 gets you as far as differentiation from cilta-cel?

Yes. Very good questions. Thanks, Matt. So with regards to the data that was presented at ACTRIMS from the Stanford team, I think overall, encouraging data. They're showing certain correlations between pharmacodynamic markers, and there's early observations on the disease score in these patients. The challenge, and this is goes back to the answer I gave to Salim before, the challenge is that obviously part of those disease scores also include patient assessment and physician assessment, 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 look -- 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, presence of the product in CSS, those types of assessments that you'd be looking at and then obviously, 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, would be premature in the early time point 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.

Our next question comes from Roger Song with Jefferies.

This is [ Fiona ] up for Roger. Congrats on the quarter. So I understand that you will shift to a positive gross margin this year. And how should we think about the near-term on involvement of gross margin once it turns positive? And with your partnership with Soliris platform 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?

Yes. 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 2 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 2 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 Soliris opportunity is obviously one where we do a feasibility study to see what the comparability of the data between the 2 different manufacturing setups, which is from an operating setup slightly different. But obviously, the biology that you're running is the same biology in the 2 systems. For us, the particular interest is actually in -- 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 the -- 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 the out where we're going to 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 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.

Our next question comes from Yanan Zhu with Wells Fargo.

Just maybe a follow-up to the primary MS study questions earlier. The study has 3 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 kind of dose response on some of the metrics? And if you could be a little more specific on powerful success, that would be very helpful. And I have a follow-up as well.

Okay. Thanks for joining Yanan 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 blood-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 sort of 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 sort of a measure of the ability to actually cross the blood-brain barrier and going to the compartment that we know that 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 where -- 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 will be, as I indicated, predominantly around the product properties in terms of expansion, the 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, 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 will be very -- an early peak, but then the much more relevant data during the course of 2027.

Great. That's super helpful. Then on the B-ALL launch for AUCATZYL, 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?

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 1/3 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 are currently looking for as an investigator-sponsored studies where those investigators are interested in exploring the use of obe-cel 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 a consolidation, but do, in essence, have an ability and look at a population or 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, 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 treatment. 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.

Our next question comes from Emily Bodnar with H.C. Wainwright.

I guess how much additional follow-up and durability data should we expect from the CARSLYLE trial later this year for the 50 million and 100 million cell doses? And what are you kind of looking to see to gain additional confidence in the LUMINA trial?

Yes. Thanks a lot for joining, Emily. So the CARSLYLE 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 6 and 12 more months, depending when the exact data count happens. So we're looking at somewhere in the range of 1.5 years to close to -- well, probably around 1.5 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 LUMINA study, the difference with the LUMINA study is that the population is slightly different. In the CARSLYLE 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 -- in the LUMINA case, it's a CD20 or other B-cell depleting antibodies and calcineurin inhibitors being after those [ 2 lines ]. And at that point in time, you actually get sort of 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 indeed, this type of an approach has an ability to improve the outcome. So it's a different definition of the patients. 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.

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 8 when we have the KOLs talk to us about the ALL disease setting of 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 I wish you all a good time.

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