For attending Jefferies Global Healthcare Conference. My name is Kelly Xu, a senior analyst on the biotech team here. For this first at-a-trip session, we are very pleased to have Dr. Christian Itin, Chief Executive Officer from Autolus Therapeutics. Welcome, Christian. Thanks for having us. Maybe to start off, could you please give us an overview of Autolus Therapeutics as of today and compared to one year ago? What have been the achievements? Yeah, I'm happy to do that. First of all, welcome everybody. Thanks for your stamina towards the end of the conference, which I know is a tough thing after a few days of activity. We got a very intense year behind us. We got our lead product approved during the course of last year at November 8. The product is called AUCATZYL, the original name, obviously, obe-cel. The label we got was in patients with relapsed refractory ALL. It's the adult population. What was unusual about the label was that it was the first CAR-T that got approved without a REMS obligation, which is reflective of the safety profile that the product has, which clearly sets us apart from sort of the competing products in the space. We're in the process. We're prepared, obviously, for launch. We're launching. We We have been initiating the launch at the end of last year and are going now, I think, very strongly as we go through the course of this year. We have, at this point, about 40 centers that are active. We expect to have 60 centers active by the end of the year, which gives us approximately 90% of patient access across the U.S. Within the centers, we have about 90% of the lives covered. The market access team has done a fantastic job and made sure that every patient who was interested in getting actually on therapy actually also had an opportunity to do so and had the reimbursement required. That was, obviously, quite remarkable. One of the important things as you launch these types of products is that it's not just actually that you deliver the product to the clinic and the clinic does the job, but you actually have to qualify the centers. In addition, you're literally providing a set of services to the center, supporting the arguments on the reimbursement side, supporting the physicians. There's training involved, product management, all the way to patient support. It is quite a range of activities there. All of that actually needs to be established, those services, and the systems behind it need to be established. As you start up, there is quite a lot of systems and processes you literally turn the switch on and you have to get going. Obviously, one of the key parameters, in addition to the commercial systems, is, of course, the manufacturing side. What we've done, obviously, through the course of last year is go through a very rigorous set of inspections by the MHRA and by the FDA and have our own facility, which is located in the U.K., and gives us, obviously, a high degree of control over manufacturing, which is critical. When you think about what can go wrong in these types of launches, and what we've seen go wrong over the last few launches is there are issues related to the quality of the product, the ability to supply at scale, the systems to book. When you think about that, that obviously has a huge impact for the centers in their ability to deliver care, creates a lot of work, and also has created, in many of the launches, quite challenging situations for patients who have obviously had high hopes, may not have gotten access to the therapy, or did not get actually productive within specifications. That is sort of the backdrop. Our focus for the last few months clearly was on making sure we are delivering to the quality, we are looking to support our customers as best as we can, and really focus on execution because that has been a real challenge in the space. There is a lot of complexity involved there. So far, knock on wood, we are moving very, very well. We're excited about the level of interest that we're seeing at the centers, the physicians, the patients to get access to product. We're excited for the next quarters as we go through the latter part of this year, but very pleased with the momentum that we actually have gained. Fantastic. Super helpful. Maybe since you have launched for several months, what are the key product features that the physician community mostly appreciated in adult ALL? If they make a switch from another CAR-T already in the market for several years, what would be the top reasons? Yeah, one of the challenges that you have with adult patients in acute leukemia is that they tend to actually have a lot of comorbidities. They tend to be frail. Part of that is due to the fact that the disease itself actually makes you immune compromised. To make matters worse, you obviously get treated with very intense therapies and particularly high-dose chemotherapy, stem cell transplants, and so on. These patients are quite beaten up. The problem that you have when you're at that stage is that it's actually difficult to sustain and sort of manage through adverse events. That has been one of the fundamental challenges that we had in the space because you need, on the one hand, an extremely high level of activity to cope with quite often the explosive growth of the disease. At the same time, you have to make sure that the adverse event level actually stays low so that the patients can really tolerate the therapy and really manage it. One of the key, I think, attributes that are very quickly experienceable for the physicians and the patients is the safety profile. We had two elements there in terms of the design of the product and the design of the dosing that we are using. The design of the product is such that we have an ability to engage the target cells in a way that delivers the kill but avoids overactivation. That is at the heart, and that is inbuilt in the design of the receptor itself. The second aspect was particularly for adult patients with acute leukemia, and actually only for adult patients. We're doing a different approach with everyone else, is to actually adjust the level and how we dose to the level of tumor burden that the patient has. That actually has been really important because what you can do with that, by patients with high tumor burden, you dose at a lower level so that as the therapy burns through the disease, it doesn't do that in an extremely fast way. By actually moving through that somewhat slower, you reduce the overall adverse event level in the patients, and it gives the physicians a lot of control. The other aspect is that before you dose, you already determine the level of tumor burden at that time, and it already tells you with a high degree of precision what the patient is likely to experience. Overall, when you look at the profile, we have about a little bit more than 2% of the patients that can experience high-grade cytokine release syndrome and about 7% high-grade neurological toxicities or ICANS. That is very low compared to any other T-cell mediated approach, whether this is through T-cell engagers or CAR-Ts. That is immediately experienceable. When you dose within a short period of time with other types of approaches, you get very quickly these adverse events. The centers very quickly, within a day or two, know how different the product actually is. That creates a lot of confidence and creates a lot of confidence with the physicians. It is a remarkable experience for the patients because most of our patients do come from prior transplant. Going through the conditioning regimen for transplant and transplant is quite a horrific trip that you go through with a lot of adverse events and quite a lot of drama quite often. To be able to go on a very active therapy where you, from your sensation perspective, have very little sensation of that therapy is obviously a huge differentiator. As you sort of start to look at three, four, five months out, you start to get a good feel for the impact the product had. Obviously, you also see that when the product also persists over time, that there is a high probability for longer-term outcome. I think that is sort of, as we see the engagement with the centers, we see kind of a lot of very positive momentum building based on those experiences. Very insightful. While we're thinking about launch trajectory, in Q1, you booked $9 million sales. How should we think about the rest of the quarters in 2025? Right. So we've been very careful not to give guidance on revenue. The reason for that is that the launch actually has several elements where you would expect an element of acceleration. Obviously, the first one is it's the numbers of centers that are open. The more centers you have open, the more patient flow you can generate. That's an obvious one. Within each center, you tend to actually start with one or two physicians that actually provide the therapy. Quite often, if it's a larger center, you might have five to ten physicians actually treating and caring for these patients. You actually have also more and more of those physicians over time that start using your product. The third element is that when you have a new therapeutic approach that you offer in an indication, you tend to first actually use that therapeutic approach for patients that are in very poor condition. You have nothing else to give. That is how you often start. As you gain information and evidence, you then actually start to expand and go in better and better patients. Even with that, you actually increase the range of patients you consider for the therapy. We have seen that actually play out in the pivotal study where one of our first physicians who treated a patient on the pivotal study was a physician in his 60s, a few decades of stem cell transplant experience. He started actually using the product for a patient that was transplant ineligible because there is nothing else he could offer. It was an 80-year-old patient. He had made very good experience. Safety was good. The outcome was fantastic for that patient. Then he started to actually move more and more into younger patients, fitter patients, et cetera, until he basically covered the entire range. That is quite a typical journey. These physicians are used for their patients to pass away. They have to be very hard-nosed about data, about facts. Actually, that experience is a critical parameter. Those are several elements in the dynamic that we have. That makes it actually non-trivial to project the actual launch itself. Internally, we think we need at least three quarters to, even for ourselves inside the company, get a sense and narrow the range of the trajectory for the launch. What we can say is we're clearly out of the gate in a very, I think, very good way. We see very positive momentum. It is sort of reflected also with sort of the consensus amongst analysts as well. We're performing, actually we're performing very well against that. We are very positive. We are very encouraged by what we're seeing. We will keep you updated as we're sort of getting our next quarters under our belt. I see. I guess you would not agree with some speculative thoughts in the past since most of the CAR-T therapies are actually launched by pharma. There was a speculation that maybe it will be very challenging for biotech to launch a cell therapy product. Yeah, I mean, that was certainly an overhang that we were dealing with is because even the larger organization had challenges to deliver the complexity that I explained upfront and what you need to do to deliver. It is very much a show-me type of situation. We are very pleased with where we are and how things are going. Maybe if you could share some manufacturing metrics of performance. In real world, what is the manufacturing success rate? Since you have manufacturing in the U.K., logistically, maybe how much longer time you would add for the vein-to-vein time compared to manufacturing actually in the same location for the infusion centers? Yeah, so the experience that we had in our pivotal study was that we have about 5%-6% of the products that we were manufacturing were out of specification. So it was very low. We see, obviously, early days on the launch, but we see that we're tracking very nicely along those lines. We believe that we have very consistent quality and are reproducing our experience that we had in the clinical development very nicely. The turnaround time is an interesting thing. There is a sense that if you're sitting on the other side of that water between the U.K. and the U.S., that it would take an awful lot of time to get there and would add an awful lot of time on the logistics. It actually does not. One of the interesting things when you think about what adds time and logistics is if you have to run relays. Most of the places in the U.S., you will have to run relays no matter where your manufacturing site is. You will relay through other cities or other airports to come in, which adds substantial time. What's very important is reliability of the transfer. Most of the larger cities in the U.S. have multiple direct flights to London Heathrow per day. That gives us actually ample opportunity for the shipments. It's one leg for most of these flights. Reliability and predictability when the product comes is actually at least as important or whether you might have an hour plus or minus in terms of transit time. What we are doing on the way back is we have an opportunity to actually ship product into the U.S while we're finishing the release for the products and then actually have the product go from a depot, which is with our partner Cardinal Health, then actually go basically the final miles to the hospital. The logistics actually doesn't add any significant amount of time here. So far, also with all sort of the movements that we're seeing on the political side, we don't actually see an impact yet from a practical perspective at the sites of entry in the U.S. We're obviously monitoring that very carefully. At this point in time, we don't think we have a difference in the turnaround time compared to a situation when we would actually run the operation here in the U.S. Super helpful. I think now we can say obe-cel is a truly differentiated CD19 CAR, especially on the safety front. Where do you see the opportunity to expand indications? Maybe you can also comment on the other ongoing trials in pediatric ALL, for example. Yeah, so one of the things that obviously, as we talked about, is very obvious with obe-cel or AUCATZYL is the safety profile, that immediate experience. What drives a lot of excitement with the physicians is the fact that we're having a significant proportion of patients in long-term remission without subsequent therapy. That is qualitatively a different outcome. That is what resonates probably most for the physicians, that opportunity to get to long-term outcomes. Now, we're going to provide an update at EHA in give or take 10 days on a longer-term follow-up with close to three years of median follow-up. At that point, that level of follow-up gives you a very clear indication of how indeed the outcomes are actually tracking. I think it'll be very positive presentations that we're going to have. We have two orals and two posters at EHA. That's where a lot of the excitement comes from. You may remember we also showed that actually adding stem cell transplant post obe-cel did not improve the outcome for patients, which was also first actually in the field. The indicative is that maybe that's something you should not be doing. That's kind of where we are in terms of that side of the equation. As part of the approval, we also have an obligation to develop in pediatric patients. That trial is progressing well. It's a smaller trial. We're going to have the data from that trial at ASH at the end of this year planned to present. What we are looking to do is, and what we are in conversation with, is to see whether there is an opportunity to actually move more forward in the pediatric setting to actually expand the label and go for a range that goes from kids all the way up to old age as sort of the age range that we could actually tackle. This is still in progress. The conversation is ongoing with the agency. We will obviously keep you updated on the progress there. Where we have made very nice progress is on the autoimmune side. We have an initial set of patients that we treated that had systemic lupus. Most of these, all of these patients had kidney involvement. These are very advanced patients that we were treating, quite different from some of the early academic experiences. We see very significant levels of activity, very quick impact on the overall condition of these patients. What we also see is that in a proportion of the patients, we also see improvement of their kidney function over time. We had half of the patients, even with very limited follow-up, show actually a complete remission, renal complete remission, which obviously was very encouraging when we keep monitoring these patients. The path forward is going to be to focus on patients with lupus nephritis, which is the majority of SLE patients with advanced stage disease who actually have kidney involvement, focus on lupus nephritis, and go into a patient population that actually has exhausted the current therapeutic options. These are patients that have gone through the B-cell targeting agents. These are a set of monoclonal antibodies from Benlysta, Saphnelo, and then the CD20 monoclonals. You also have failed on calcineurin inhibitors. Now you are in a situation where you have kind of exhausted the therapeutic options. At that point, you have an opportunity to actually run the trial as a single-arm trial. By focusing on lupus nephritis, it also gives us an ability to focus on a hard endpoint. This is actual filtration function of the kidney. That is a biochemical measure that you can actually do. The beauty of that is it is an objective endpoint. That also allows you to then actually keep the study size relatively compact. We are currently planning to enroll 30 patients into that or treat 30 patients into that study. That is a very unusual approach in that regard. What is obviously important is 30 patients would not be enough to discharge the safety considerations. What we obviously do have, because we have an approved product, we have a large safety database from our leukemia work. And that safety database actually supports the activities, obviously, on autoimmune, which is why we do not have an obligation to go beyond that trial to actually have an appropriate level of data to then consider moving forward. A very important, I think, opportunity here. We are also obviously going to record our secondary endpoints, SLEDAI scores, et cetera, which look at other manifestations of the autoimmune disease. A lot of these patients have rheumatoid arthritis, have skin issues, have other organs impacted. Obviously, you will record that as well. That is what we are doing in lupus nephritis, obviously moving into a pivotal study, which plans to start that trial second half of this year. We are also running an exploratory trial in patients with progressive multiple sclerosis. The hypothesis there is that the B-cells that are involved and drive the disease may not only be resident in your bone marrow and in your lymphatic tissue, but they also may be present in the brain itself behind the blood-brain barrier. One of the remarkable things about CAR T- cells is that they actually manage to cross the blood-brain barrier very efficiently. This is not a hypothetical for our product because we have treated patients with primary CNS lymphoma. We are able to show that indeed in primary CNS lymphoma, we can actually get very significant levels of activity. Also on the acute leukemia side, you do actually have a lot of patients that have extramedullary disease in the CNS. We can also show that we are active against that disease. We know the product is very active. It has obviously a very good safety profile. We are looking forward to running this exploratory study and to see whether indeed that type of a reset could actually transform the outcome for these patients. That is clearly a question we are asking. It is also a scientific and clinical question. If answered positively, I think it could open up a very significant opportunity. Very exciting. Maybe can you also comment on do you plan to talk to regulatory agencies and thinking about a pivotal trial design for both lupus nephritis and in the future multiple sclerosis? Yes, the conversations for the pivotal study in lupus nephritis happened. What I'm talking about is actually based on conversations that we have with the agency and the input that we have received from the agency. Multiple sclerosis, obviously, we need data. With the data, we're going to definitely have those conversations. That is data-driven interaction. We already see some feedback from regulatory agencies in this space. Curious your thoughts on do you see accelerated paths and a single-arm trial actually across different indications? Or is it also determined by unmet needs and also available therapies across different autoimmune indications? Right. Look, the regulators take a very rational approach. It's actually almost independent of the actual disease setting. The first thing is if you think that a single-arm trial is what would be appropriate, obviously, you have to have a very high medical need. You have to have exhausted all other treatment options. You have to have a very high treatment effect. In very simplistic terms, you have to think that you're going to be at least twice as good as anything else that could possibly be given to these patients, very simplistically. OK? That's true for if you go through oncology and you go through all these single-arm trials, that's sort of where the primary endpoints were pegged at. That's kind of the requirement. If all of that is true, then I think running a single-arm trial is sufficient to demonstrate that indeed you have an adequate level of activity that gives you the level of confidence that indeed the outcome you're looking at is real. That's what that is. That's the stats behind it. If you have obviously a limited level of activity, as we've seen in lupus with monoclonal antibodies, where you eke out a four-point improvement in a SLEDAI score, at that point, you need a randomized control study because that's just not enough of a signal. You need a large sample size to actually be able to show that there is a statistical difference between the curves. Or at least you can hope it does. At times, that was true. At times, it was not. It is very much down to the actual treatment effect that you actually can get. If you fulfill all those requirements with high treatment effect, et cetera, then that is a possibility. I think there is an openness to then actually consider that. You would still need to have enough safety data to sort of support that. Typically, what we have seen across the board for high medical need settings, et cetera, is at least 100 patients' worth of data, which has been quite consistent across the last 15 years- 20 years, kind of what was required. Those stats behind that are pretty steady. I think the agency has been very consistent in the way they have been looking at that. Yeah, pretty easy to follow. Maybe lastly, could we reiterate the key catalysts and milestones in the next 12 months from Autolus? Right. First off, obviously, we're in a, as I mentioned before, we're sort of in a show-me place. We have to prove that we can actually sell product. OK? That's kind of the primary focus that we have to make sure that indeed we can deliver on the launch. That's the first. The second is, obviously, we have data at EHA and then at the end of the year at ASH related to the leukemia program. We're planning to have updated data from our SLE phase one study that we're looking to submit for ACR. Obviously, as we go into next year, I think that's when the pivotal studies should be on the way. We're looking forward to keeping you updated on that. Fantastic. We are going to wrap up here. Thanks, Christian, again for a super insightful discussion, as always. Thanks, everyone, for staying with us. Thank you. Thank you.