Good afternoon, everyone. My name is Clara Dong from Jefferies Biotech Research. Thank you for attending our healthcare conference in London. We're very pleased to have Dr. Christian Itin, CEO of Autolus Therapeutics, joining us today for this fireside chat. Welcome. Well, thanks for having us. So maybe before getting into the approval of Aucatzyl and other programs, maybe we can start from the high level. You know, what's been going on for the company over the past 12 months? Yeah, so obviously the last 12 months were very much focused on getting through the approval process. That was kind of front and center with what we've been doing. Obviously, a lot of activities related to that. This is Aucatzyl therapy, our lead program that just got approval on November 8. And that requires you to have actually quite a bit of infrastructure ready for launch. You require, obviously, your manufacturing infrastructure to be set up, fully evaluated, and ready to go. A lot of data generated around that went actually into the BLA filing. And so as we went through the year, very heavily engaged with, first, actually the MHRA to sort of get the initial license for the facility to operate it. Secondly, obviously, very significant interactions with the FDA, with site inspections, but then also obviously very involved in the full analysis of the manufacturing process, performance. In parallel, we were obviously going through all the clinical data and the data integrity checks, et cetera, which is quite involved, actually, leading up to the PDUFA date on November 8 and getting a week early to an approval, which is quite unusual, actually, in this space, given the complexity of the operations and what you actually all need to get cleared. Most of the programs in this space had significant delays, a lot of them related to CMC or the capacity, et cetera. To sort of get through that actually ahead of time and with a very good label has been fantastic. We're very pleased with the outcome. Big congrats to the approval. Now that Aucatzyl is approved in the U.S., so could you please give us an overview of what kind of efficacy and safety data is on the label and how does it compare to the available standard of care in the disease? Right, so what's interesting, obviously, about this indication is that these are highly immunocompromised patients that we're treating. They've been typically through initially high-dose chemotherapy regimens, might have actually seen as part of the consolidation, might have seen Blincyto already, the T cell engaging product from Amgen, and have relapsed after that. Many of the patients have not only just relapsed after front line, many of the patients we had in the study also had gotten second line therapy, even third line therapy, often including stem cell transplants and failed after that. And as you can imagine, as we went through the pandemic, a lot of these patients were heavily advanced in their disease. And everybody was really concerned about actually having these patients travel to the institutions to actually be treated. These are highly immunocompromised, huge risk of infection. Quite often the cause of death for these patients is sepsis. So what we were basically having in the study as we were rolling that study was we're rolling through the pandemic. And we had, in essence, a real-world setting of patients. We also, as a company, were not able to actually go to the clinical sites. So even from that perspective, it was hands-off to a degree, which is not for the faint of heart to actually deal with these types of patients in that type of an environment. What's very remarkable about the data is that we were able to replicate the data we had actually generated prior to the pandemic. In a smaller trial here in the U.K., we were able to replicate the safety, which was quite remarkable. We have a 2% high-grade CRS, 7% high-grade ICANS in our patients, which is a remarkable outcome given the patient population and also given the level of tumor burden that these patients had. So many of these patients had very significant levels, more than 75% tumor burden, a lot of them at the 90%-95% range. That's very, very difficult to manage the patient, but it also creates a very difficult starting material when you collect the T cells because those cells tend to be in extremely poor condition. The other aspect, of course, is that as we were looking at these patients, because the patient, the safety profile was actually very favorable, we also actually had a lot more older patients involved, and typically, older patients with this disease tend to be very frail, and they're often excluded from very active therapeutic modalities. They're often actually excluded from stem cell transplant, and it was very interesting to see that our median age in the study actually was higher than comparable studies actually have been by about 10 years, so our median age was 51 years in that study, which was quite remarkable in its own right, and then with regards to activity, the important part that we had to do, given that we were part of the pivotal study in the pandemic, we did not limit the ability of a physician to control and manage the patient from a bridging therapy perspective. To take a step back, these patients obviously come in, they actually get connected to an apheresis device and you collect the T cells. You then go into manufacturing with these T cells, and it takes time, obviously, for the manufacturer and the product to come back. So during that period, which in the study was about 21 days, you need to manage these patients. And to give you a flavor for the intensity of the relapse that many of these patients experienced, we had patients that went from below 5% tumor burden to above 75% in 21 days. Okay? And this is with everything you could throw at the disease, it would kind of get us that level of out of control. So we actually allowed the physicians to use any type of bridging therapy, including inotuzumab, because frankly, we didn't know what the condition would be that this hospital would have at that point in time in the pandemic, the patient would face. And so you cannot actually be in a situation where you tie the physician's hands behind his back and say, okay, go manage. So that was important because the importance was that out of the patients that we have actually dosed, there's a proportion, which is quite sizable. It's about 23%-24% of the patients actually dropped below 5% tumor burden, and those were excluded of the analysis. Now, what we know from the ASH presentation last year is that those patients have an exceptionally good outcome. So with 65% event-free survival, which means they're actually stable and with a high likelihood actually in long-term remission. Now, if you look at the rest of them, the rest of those patients is at least as good as any of the other products that have been prescribed from an efficacy perspective with a much better safety. If you take the integrated look, you realize that in fact, the product has a substantially better outlook for these patients with an ability to support patients' long-term outcome without any subsequent therapy. So that's sort of where we are with the product. Fantastic label. What was very important though as well is that this was the first product in this field that got approved without a REMS obligation. So there was no requirement to actually collect the immune-related adverse events in a special database. The importance of that is, first of all, it takes a certain level of reassurance that the agency needs to have to do that as a first of its kind. But secondly, it also actually has very practical implications for the centers. That data collection is actually real work because you actually have additional data you need to collect, you need to actually put it in databases. It's work for the centers, it's effort. And to actually be able to reduce that is very important. And when we think about moving beyond the acute lymphoblastic leukemia space, which is obviously a highly, highly specialized area, obviously that becomes even more important because those other types of indications and situations, the physicians are not used to actually dealing with REMS programs because it just isn't necessary for those types of therapies that are typically available there. Fantastic. So let's talk about commercial preparation. So could you please talk about on a high level, what's your commercial strategy in the U.S.? When do you expect to launch a product? And And how many medical centers are you targeting in the early phase of launch? And maybe also more color on the pricing because you do have a premium pricing of around 14% premium to the available therapy. So what's the rationale for that? Yeah. So in terms of the preparation for launch, this is obviously an activity we're on for quite a long period of time. So when the label got in, literally within about 20 minutes, the commercial team was actually out and moving. I'm not kidding. This is the level of preparation we had. When you think about this space, it's quite different from many other indications in that the patients at that stage of the disease tend to get actually treated in a relatively small number of centers across the U.S. So about 60 centers cover more than 90% of the patients. And this has to do with the fact that these patients tend to actually have a lot of comorbidities, are very challenging to manage, so it takes a lot of expertise to do that. That's concentrated in these 60 centers. Now, we have actually 30 centers that were ready for activation at the time of the PDUFA date. We're going to add an additional 30 to get us to the 60 centers during the course of next year. Now, what does that mean to activate a center and get it ready? Actually, this is a very involved process because you actually have to prepare the center from a reimbursement support perspective, from an apheresis, a collection of cells and cell handling perspective, safety management perspective, but then also a very significant amount of contractual relationships you have to put in place to actually make sure the center is in a position to deliver this type of therapy. That's a 6 months-12 months process for each center to get ready to actually be activated. Now, we had 30 centers at the stage where all of those work, all that work stream was completed, and then you have the final step, which is actually the step you can only do once you have an approval. You need the label. Once you have the label, you have to do a final set of training with the center. That's very quick. That's half a day, a day max, but after that, the centers need to actually take this new therapeutic modality onto their formularies, onto their administrative processes, which they can only do once the product actually is approved. That's obviously a legal issue, so they need to work through that and actually get it into their system and integrate it with their system, and that takes anywhere from two weeks to several weeks to get that done. We expect as we get into Q1 that those 30 centers will actually be available and ready to actually enroll patients onto the product. Then the additional 30 centers are obviously in varying stages of progress on the onboarding process, but they're all actually in motion. That's sort of kind of what is involved to actually get that going. What you need to establish is obviously a series of services that support the center to deliver the therapy. Those services include, as I indicated, it includes support at various levels, whether it's at the physician level, at the administration level to support with the payers, to support the patient on travel arrangements, et cetera. There's quite a range of activities to support the pharmacy within the hospital. Now, in order to then manage all of these processes and particularly manage the course the cells are taking from collection all the way through logistics to our factory to get modified and manufactured, and then on the way back to the patient, you need a cell orchestration platform because you need to absolutely control every step along the way, and you need to be able to make sure that there is no ability to actually miss or allocate any of these products. So you need a complete chain of custody that needs to be thoroughly also evaluated and set up. That's actually an IT system that's bespoke. So all of these things have to be put in place. And in parallel, you support all of those activities with MSLs on the medical affairs side. So those are kind of the activities that go into activating. And then with regards to the price, the price is correct. It's at a premium to one of the other products, but it's also below one of the products. So Kymriah is priced in the U.S. at $582,000, the other competitor product at $562,000. So we're sort of in between the two. One of the advantages we have by having this very good safety profile is that we have actually much less resources required to manage the patients, much less cost to treat these patients. So the overall cost proposition is economical for the payer at these levels. And so there's a lot of work that we've done to actually evaluate the price level and the acceptance around that. Fantastic. And I also want to briefly touch upon the split dosing protocol and how should we think about the implementation of such protocol in a commercial setting and how should we think about it from the insurance reimbursement perspective and what's the feedback you've received from physicians regarding this split dose protocol? Right. So one of the key drivers of toxicity in these patients is the level of tumor burden the patients have. And the biological problem is that the tumor is located in the bone marrow, and it can fill out literally up to close to 100% the marrow. So every cell can be actually a leukemic cell. At the same time, the T cell biology is that when you put the T cells in, they actively home into that compartment, which means you get a maximal engagement between incoming T cells and easily accessible target. The problem with that is you get an enormous amount of kill, and your kill rate, ultimately the amount of kill and your kill rate is determining your tox. What we have devised is an approach where we actually address the level of dose that we use to the level of tumor burden, and we give the physician the ability to control the process to the maximum extent. That's something that we actually learned from the development of Blincyto product that I had the chance to work on before. What we did with Blincyto was we had to first actually reduce the level of tumor burden by giving a lower dose. After about a week, we would actually be able to do triple the dose and then actually sustain that dose level. That was designed to actually minimize that initial actually rate of killing so that we get to a point where we can then actually clean out with a higher dose later on without pushing the tox too much. We've used the very same principle actually here as well. So we give a first dose, we do tumor adjusted dosing. So depending on the tumor burden that we have in the patient, we dose accordingly and then actually give after 10 days the second or remaining part of the dose and then actually let everything go. The physician is in control, and the physician can control whether or not to give the second dose. So if you have a patient that actually has developed major adverse events or an infection or any other issue, you actually have an ability to withhold that second dose and with that make sure that you manage the patient accordingly. Putting the physician in charge and in control is critical. So the product is actually delivered as in one go, and then it's the physician who makes the dosing decision. It's basically two modes that can be done, and that is analogous to what they're already used to doing. The charge actually is on first dosing. That's when you actually recognize the revenue. That's actually when the payment actually gets triggered, and when we look even across the clinical trial, we have way above 95% of the patients receiving both doses. Gotcha. And also what about manufacturing? What's your preparedness for manufacturing and in terms of the product release criteria? What kind of do you expect any difference in commercial setting compared to the clinical trial? So manufacturing is absolutely essential to control in this field. The manufacturing process defines your product. And so you have to do basically two fundamental things. The first is you have to actually create a manufacturing process that can actually deal with the variability of the incoming cells. And as you can imagine, if you have cells that come from a patient who's basically off high dose chemotherapy, it's one thing. If it is a patient that has circulating leukemic cells at a high level, that's another issue. Or you have actually a patient that has virtually very little disease burden and the cells are in decent condition. So you have a wide range of incoming quality of the material. And what your process needs to do is take that high degree of variability and create a product with a defined set of specifications. So it requires a very significant amount of work to actually make sure you get that level of consistency. That gives you robustness in your manufacturing process. One of the key issues that many of the processes had in our business is they were not robust at the time of launch. We had about 500 full scale runs done just to give you a sense of how involved that is to actually nail this. Now, the second part is you have to actually be able to do this at an industrial scale. And the problem here, of course, is it's an individualized therapy. Each patient is one product, requires independent release. So in order to actually get economies of scale, you need to be able to parallel process. So critical for that is, number one, you need actually a level of automation. Number two is you need a manufacturing process that's fully enclosed so you can actually run a lot of these pieces of equipment in the same environment and with that realize economies of scale. We've done that. We're building on the Miltenyi Prodigy platform as the machine that we're using, and then obviously with a highly optimized process on it. This allows us to run clean rooms that give us actually a pretty sizable level of output. Each one of our clean rooms is about 700 batches per year output. We have four of those rooms in our commercial manufacturing facility that sits 20 miles up north from where we are here. The importance actually of having that facility is it allows us to optimize every aspect of that manufacturing process and operating model. That's critical to reach attractive cost of goods. Having an ability to operate at scale, at quality, and at a good level of cost of goods is critical in this business. You only control that if you actually have that developed and set up for your business and for your product. That's critical. It was a huge lift. We started actually with a groundbreaking on November 8, 2021. We got approval November 8, 2024, exactly three years later with a newly built facility fully validated, giving us that level of activity and capacity while we were running the pivotal study through the pandemic. One of the things we did is in June or July 2021, we bought steel for few million bucks. You don't want to do that as a biotech company, but that turned out to be really important when you think about the supply chain issues we had during that period. Anyways, that's an aside. Fantastic. So let's move on to your development in SLE. So could you walk us through how does obe-cel differentiate versus several other CAR-Ts currently being under evaluation in SLE? And given FDA recognition of the optimal safety with REMS on the label, what kind of read-across should we expect from the adult ALL to the ongoing trials in autoimmune diseases led by SLE? So the reason why we're excited in the space about the opportunity to go into autoimmune disease is that there's an observation that goes back to a German academic team, Georg Schett and Andreas Mackensen at the University of Erlangen, who actually observed that if you actually treat patients with advanced stages of lupus mostly initially and then other sets of autoimmune diseases, you actually had an ability to not only reset the B-cell compartment, but also get rid of the plasma blasts, which turned out to be the cells that actually were producing the autoreactive antibodies that were driving these diseases. Remarkable observation, remarkable from a biology perspective, remarkable outcomes. Now, where we are is we have obviously the only product in the space that actually has a label anywhere that goes and is active now, actively developed in the autoimmune setting. We have obviously the commercial manufacturing base and capabilities, but more importantly, we have a really significant safety database. The fact that the agency in the context of the most challenging indication you can actually develop a product in, which is acute lymphoblastic leukemia, have the conviction that we don't need a REMS tells you something about the perception of the safety of the product. That is important in autoimmune disease because this is a different type of tox. They're not used to the level of intensity of therapy that a hem-onc physician would be used to. Hem-onc physicians are remarkable in terms of what the confidence they have of what they can manage. That's different if you're in rheumatology or in other areas, so having a product with a very good safety profile matters. We'll have data at ASH coming up where we actually show the level and depth of response we can induce in ALL and the impact it has on outcome. That level of depth of response will tell you an awful lot about how potent the product is and how good this product is at resetting the B-cell compartment, so we'll see those two components are critical, and now we're exploring the product's activity in SLE patients. These are all very advanced patients, and we certainly will expand into additional indications as well, but having the only approved product in the space puts us in a very different situation than the other programs currently underway. Terrific. And your first SLE patient was dosed in the second quarter of 2024. So could you talk about when should we expect the data and what kind of data will we see from the next update? So we expect to have early data from an initial cohort of patients that we have been treating with dosing six patients at 50 million cell dose level. That data is expected as an early data set at the end of Q1 and then full data with long-term follow-up and understanding the dynamics, the cellular dynamics in full towards the second half of the year. So that's sort of the trajectory currently that we're projecting. Great. You also have a CAR-T AUTO8 with dual targeting to CD19 and BCMA. So could you talk about the status of this program and when should we expect an update? Do Do you plan to explore autoimmune opportunity with AUTO8? AUTO8 is a BCMA CD19 targeting product. That's your complete wipeout of the plasma cell compartment and the B-cell compartment. Now, where that matters a lot is obviously in multiple myeloma. That's one area where we have initial data and we presented that. We're exploring other plasma cell disorders, and you could possibly also consider that in autoimmune disease. You would want to be careful about that because that very profound reset also means that these patients lose actually all their immunization status because you literally wipe out all of the plasma cells in these patients as well. Unless you have a good reason for doing that, we wouldn't do that. So currently what we're doing is we're focusing on CD19, which allows you to protect the immunization of the patients and gain information about what are subsets of diseases where actually dual targeting may be needed. The good thing is we have a product to do that. But at this point in time, we're focusing on other types of plasma cell disorders. Fantastic. And lastly, could you remind us what are the key events in 2025 and what should investors be focusing on for the next 12 months? Right. So on the regular, obviously the launch itself and the progression of the launch, that's a base. We have under review, the program under review with the European agency and the MHRA. So we expect to go through the final steps of the regulatory process as we go through the course of the year and then launch actually in the U.K. and do a first launch in Germany hopefully by the end of next year. And then when we look at data, we have pediatric data coming up middle of the year. We have the second half of the year on the SLE data, and there's going to be quite an additional set of information publications and data releases around the adult ALL program as well. So that's the core. And then there may be a bit of an extra depending on some of the earlier stage programs and translational activities that we have ongoing. Fantastic. And we will wrap up our session here. Thanks again, Christian, for spending time with us. And thank you everyone for attending our session. Thank you very much.