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.