Hello. Good morning. Welcome, everyone. This is day one of Jefferies Global Healthcare Conference. My name is Fiona. I cover med tech, biotech companies at Jefferies, and it is my greatest pleasure to welcome to this fireside chat with me, from Autolus Therapeutics, CEO Christian Itin. Thank you. Welcome. Before I start grilling you with more detailed questions, how about you give the audience some highlights on how the business is going. I know you have some interesting updates at the most recent earnings. Just give us some color on that. Yeah, happy to do that, thanks for having us. Thanks for taking the time, everyone in the room. We're at an interesting point. We're now 18 months into the launch of AUCATZYL in the U.S. We had a really successful first year of launch. As you remember, our lead product is a CD19-targeting autologous CAR -T product that got approved at the end of 2024. We had in relapsed refractory adult ALL, with the indication, the label we have for the product at this point, had $74 million in revenue in 2025. We're guiding to $120 million-$135 million this year. We had a good first quarter with $26 million, we see good dynamic in the launch process. We also had the fortune that alongside our launch, the ROCCA consortium was actually collecting real-world data, which was quite unusual to see your own product perform in real time, and was presenting that data at the ASTCT meeting in February. What was nice to see is that there was a nice confirmation of our clinical outcomes, and if anything, the data looked somewhat better than what we had in the clinical trial that led to approval. Reflective of the fact that not only did we have very good safety with no high-grade CRS and only 3% of the patients with high-grade neurological toxicities, and overall less than 20% with any form of neurological toxicity, which is a remarkable profile in that space. Also see that translated also on the efficacy side, where the team reported more than 90% complete remission rate for the product in the real world setting. What it also did show is that, in fact, the physicians start to use the product in places and in situations where they were not considering CAR -T therapy before. We're seeing them go into patients that were older, patients with more comorbidities. Also about a third of the patients were treated with very low disease burden, which certainly the physicians who've part of the clinical development program have been able to demonstrate in our prior work that those are the patients that have the highest chance for long-term benefit. We see actually that already branch out in every one of these directions. The dynamic we're seeing, I think, is extremely positive, and we're building obviously on that now as we're building through the second year of launch. We're at currently about 76 centers that are licensed to deliver the product in the U.S., and we expect to be probably in the mid-80s by the end of this year. Beyond the relapsed refractory setting and adult setting, we're having actually first trials that have already started investigator-sponsored studies for frontline consolidation and frontline use of the product. All of that actually focused on getting away from a 36 months high-dose chemotherapy regimen, which is quite horrific in that disease setting, and actually go to a compressed upfront regimen that may be just four to six months. That obviously could be a potentially a very big step forward in the field, and that's being explored in two ISTs in the U.S. and one that's currently under preparation in Europe. Beyond that, we have a pivotal study ongoing in pediatric patients. We have shown at ASH at the end of last year that we had above 90% complete remission rate in that population, good safety profile. Based on that data, the agency agreed that we could actually increase the size of the study by additional 30 patients, and with that have an ability to go in for a full approval, obviously assuming a positive outcome of the study. Now, in addition to those activities on the oncology side, we've also been very active on the autoimmune side. What we do know about our product is it has a remarkable safety profile. It's exceptionally potent. It has an ability to obviously very efficiently cross the blood-brain barrier, get into difficult to treat areas in the body. On the autoimmune setting, the initial work we've done is called the CARLYSLE study, where we looked at very severe forms of SLE patients. Most of those patients were lupus nephritis patients, so they had very significant impact already in their kidney. What we did see is a massive improvement in all of these patients that were treated. Very good safety profile, no neurological toxicities, and we were able to see a very nice rebound of the B cells after the CAR -T cells stopped persisting. The cells that were coming up, the B cells were coming back, actually had a normal composition and did not actually carry autoreactivity. It looks like based on that data, with the amount of follow-up we had at the end of last year, that indeed we do get to a reset. We will have quite more substantial data at the ACR later this year, and that gives us then more patients, but also substantial amount of follow-up in that indication. Building on that, running a lupus nephritis pivotal study, which is the LUMINA study that's up and running with an agreement for the agency and the refractory population to move forward. We're very excited about that study. Mechanistically, I think the most interesting study from that perspective is the study we're conducting in progressive MS patients, the BOBCAT study, where we really leverage the unique properties of the product to be able to get into the CNS and obviously having a high level of activity. Something we know from CNS leukemia and CNS lymphoma, where in both cases we actually have data from our oncology experience. That study is enrolling. We expect an early view at the end of the year. I think a much more robust data set during the course of next year. That's in a nutshell, I think where we are with the business. That's a great summary. Definitely a lot to unpack there. Let's start with the commercial, the Yervoy in adult ALL. You're still in the relatively early stage of launch, but the U.S. revenue has been doing great and growing steadily. How should we think about the near term and long-term growth drivers? We understand there's important dynamics with the centers, the physicians, and patients. Just give us some color on that. Yeah, happy to do that. Obviously, what's unique about CAR -T therapy is it's a one-time intervention. When you think about your business and building your business and growing market share, it's not that repetitiveness or that growth is really doesn't come from a repeat business with a given patient, but it's a repeat business with a given physician. Where you need to build the confidence and the experience is with the physicians, and to grow the physician base in every single institution, so that whenever a patient actually gets to a given institution, the patient has access to the CAR -T therapy, and the physician is aware of the therapy and the opportunity that it represents. That is actually the key work that we need to do to grow market share. It's much less on the adding more centers. It's much more focused on really penetrating the current centers that we're in. What we do in terms of actually increasing the presence from a center perspective, it's more around filling in geographic gaps, as well as making sure that centers that have larger feeding centers that actually drive patient flow into them, that in those centers that have on their own a relatively high level of patient flow, that we actually established a therapy already at the center so that we're getting closer to the actual patients as well and minimize the need for patients for excessive travel. That's a key driver there. What we find is with the physicians is there's three categories of physicians that you can think of. You got the older physicians my age that would have grown up with stem cell transplant. That's the primary experience that they do have. For them to actually start adopting a new therapy, obviously that takes time, and it takes opportunity to gain experience. The key opportunity for them to gain experience is really in the transplant-ineligible patients. Those patients they cannot offer what they think normally would work in their hands. That's typically where it starts. The experience then with the patient, the safety profile, the activity level that they can observe at that, then tends to actually get them to start actually using the product in patients they would actually have considered for transplant, but are actually start to evaluating and using a CAR -T in there and gradually use the product across the entire range. That's not a theoretical comment I'm making. This is a practical observation that we're making. One of the best examples here is actually the physician who did the first patient, treated the first patient in a pivotal study, was exactly one of those older transplanters. He did treat the patient where he knew there was just nothing else he could possibly give. An 80-year-old patient, very, very significant comorbidities, neuropathies, and lots of other damage from the high-dose chemotherapy. There was virtually nothing you could give that patient without actually risking, frankly, that the patient would get worse as a consequence of the therapy. That's the first patient he treated. That patient did remarkably well. Patient actually lived for several years, eventually in his mid-80s, passed away unrelated to leukemia, was free of leukemia. Based on that experience, started to use the product actually then in patients that were younger, where he had thought he had actually options, started to use it, gain more experience. I met that physician at the ASTCT meeting in February, and he told me and said, "Look, I've treated around 10 patients at that point in time. None of them I've transplanted." Okay. That's the transition and that's the adoption that we're seeing. That's the transplant. The second category of patients at the other end of the age spectrum, which are the younger physicians that actually have grown up with CAR -T therapy and have sort of been the technology that they sort of actually were familiar with. They actually look for a better product to use and a safer product to use. They actually transition very, very quickly, and they tend to transition fully. There's an intermediate group of physicians that neither transplant nor do CAR -T. They're the ones that mostly are treating the frontline patients, so they are familiar and typically use high-dose chemotherapy, maybe blinatumomab, maybe inotuzumab as part of the overall first-line therapy. Not yet familiar with and comfortable, not comfortable with stem cell transplant, not yet familiar with CAR -T. That's the third category. We're really making sure we're addressing each one of these physicians with an opportunity to get involved, and then actually build that experience. When we look at sort of we're tracking obviously all the physicians that we have that actually are delivering product obviously have to be registered. They have to be trained. They're sort of visible to us and visible in the system. We can actually track how we see the growth of physicians that are actually using the product, how many of them actually are reusing the product as well, which gives you then the information that, yep, it starts to stick and they start to move on. We see a very nice dynamic on those parameters. Those are lead indicators that give you a sense for market share development much earlier before you see it in the actual numbers. That's very helpful, colors. It makes a lot of sense, this physician satisfaction and also loyalty is a very critical component to the revenue growth. Just follow up on that, you talk about those three buckets of physicians. Just in ballpark, what% of physicians have you seen that reuse the product? Well in the majority. Okay. This is more a question of time because we're onboarding centers. Yeah You have a leading edge. We see them all actually reuse the product. It's sort of reflective of the fact, when you think about it from a physician perspective, the fact that the product is very safe and can be well managed, that's incredibly important because, on the one hand, it gives you confidence to use it across the board, and it's a challenge when you think about these patients, they're not static. Those patients actually, if you see the patient initially diagnosed, determined there's a need for therapy. Well, by the time you treat the patient, the patient could be in a very different state. Knowing that you're actually okay to treat the patient across this entire range of possible outcomes, whether very high disease burden or maybe have responded to bridging therapy, which is a huge variability in terms of where the patient might be, you need a lot of conviction that you can manage that. The safety's incredibly important from that perspective. It also obviously allows the centers to minimize, frankly, their own resource use. If you have your staff, that's a certain number of people you have. Well, if you have severe neurological toxicity, well, your team is in the ICU managing that patient because you need to make sure the patient's getting through. That absorbs a lot of attention and a lot of effort within the center, and distracts from other patients that actually need the attention. That becomes really important. It's important for the physician. The other aspect which we shouldn't forget is, it's also very important for the hospital administrators and the financial folks at the hospitals. Actually, not having patients go into high-grade toxicity situations has a huge impact on the profitability of the product. This is literally tens of thousands of dollars. This is not a joke. The health economic aspect here is an important one to actually also keep in mind. When we're engaging with centers, our audience is, on the one hand, the administrators, the economic part of the hospital, but it's also, of course, the treating physicians, the nurses, and practitioners. Yeah. That's very helpful. Certainly, the cohesiveness of the product speaks for itself. Yeah. Now let's turn to ex-U.S. Now, understanding this is still early, but we see some encouraging signal from the U.K. side. Just tell us about, in long term, how do you see the U.S. and ex-U.S. dynamic? When do you expect to break out the ex-U.S. sales? Right. We started our launch in the U.K. at the beginning of the year. We're in the fortunate situation that NICE, when they did the assessment of the product, concluded that the product was cost efficient for the NHS. Actually was taken up, had adequate level of data to be taken up directly into routine commissioning. No further need for data generation to actually prove the value of the product. That was important because it gives us immediate access in the system. What's interesting about the system is that the decision-making whether a patient gets on CAR -T or not is taken by a panel of eight physicians. Every ALL patient actually goes through, the case will be looked at, decision will be made, what's the right kind of treatment pattern here, and then the treating physician can choose what type of product they're going to use. The decision is taken centrally for CAR -T. The consequence of that is that adoption in the U.K. is faster than the U.S., because in the U.S. we have to convince literally every individual physician. In the U.K., we have to convince eight physicians, and they're making the decisions alongside. What it also led to, which is probably not underappreciated or not really known widely, is that actually the percentage of CAR -T patients or patients accessing CAR -T in the U.K. per capita is higher than in the U.S. That's not what we normally would think of. Okay? The benefit, obviously, we have is that the U.K., you can look at the health economic benefit across the entirety of the system, and actually a treatment that can get patients to cures, long-term outcomes, is a huge reduction of burden on the system overall and can be valued. That's not true in many other systems that are kind of organized differently and do the calculations differently. I would assume that in the U.K. we're probably going to get to a point where we probably will have to break out numbers. I would assume second year of launch is my current estimate, but we'll need to see what the development looks like. It may be a bit earlier than that. We also have approval in Europe, and Europe, the situation is that you also get a centralized approval for the product. The tension you have in Europe is that the health economic models in Europe and the basis for approval, in particular when it comes to small indications and high treatment effects, is sort of dissociated from each other. The approval, like in the U.S. or the U.K., is based on a single-arm study with high treatment effect. Very clear, approvable, no questions asked, really from a type of data perspective. On the other hand, you have the health economic models in Europe that actually are built to use data from randomized controlled studies. The problem that that creates is that the model, the actual financial model, does not work with single-arm datasets. What you get in Germany and other places is then the statement that it's a non-quantifiable benefit. The emphasis is everybody agrees it's a benefit, but it cannot be computed. Okay, that's what that says, which is obviously an oxymoron in English, but it's kind of what it actually is. That's one of the issues. The models that are used there are actually not really designed to reflect the benefit that these types of therapies can actually provide to their system. That's one issue. The second challenge you have is that the way that healthcare is paid for across European countries is basically in two buckets. There is an infrastructure piece, hospital, staffing, base equipment, running costs. That's an infrastructure cost that actually is paid through taxes in most countries and is not actually broken out and not visible. What's paid by the quote-unquote "payers" then is what's left, and that's drug acquisition cost, certain diagnostics, certain aspects of treatment. What it does, it actually skews the view in terms of benefit in a remarkable way because it excludes any benefit on the resource utilization. That creates the tension in pricing, and that's where you see differences in pricing between the U.S. and Europe. A lot of that is driven by these very fundamental different principles that are being applied. That creates issues. That gets us to MFN. MFN is interesting in the sense that what we're seeing develop at this point is that cell and gene therapies are actually excluded in the current pilot. Okay? They're not part of MFN. There are certain countries, if they have made agreements with the U.S., may be excluded. That would be true for the U.K. The U.K.'s excluded from MFN. There is obviously a threshold that you have to cross in terms of amount of sales to the particular part of CMS that actually is calculated for, and that's another hurdle you have to get on. Only if you're beyond that is when MFN actually kicks in. For an indication as acute lymphoblastic leukemia, we believe there's no way, even if cell and gene would be included, it would ever actually trigger that hurdle. We're looking currently for options in Europe, and we're evaluating that, but that's a country-by-country process. We haven't actually guided yet on any European sales at this point in time. That's still premature. Yeah. Awesome. Thanks for the color. Hopefully, we see some nice ramping up in the ex-US revenue there. I want to touch on the business side. You mentioned you were going to turn margin positive in 2026, but you actually delivered that in the first quarter. What measures have you done to achieve that? Moving forward, how can you keep driving the improvement? Right. The first year of launch in a cell therapy tends to be gross margin negative. The reason for that is you need a lot of infrastructure that you have to operate, and you have a very limited number of products that are running through. When we look from 2025 -2026, we are going to double the amount of products that we're actually manufacturing. We're going to do that with the same or slightly less staff than we had last year. In very simple ways, what that does is that your fixed cost contribution year-over-year gets halved because you run twice as many products. Your staffing stays same, but you'd have twice the product, means your labor and the time you spend per product gets halved. Okay? Those are the key drivers why we're going from a gross margin that was negative last year to a gross margin that is positive this year. The reason why we could do this on the labor side has a lot to do with the fact that we've learned a lot in the first year of manufacture. What that allowed us to do is really look very systematically at the operating model and frankly any unit of operation and actually keep improving on that. Our current projection is that as we're looking at where we are with the business, that we should be able to serve even the peak U.S. market with our current level of infrastructure and staffing. That tells you how the costs ultimately will go down and why the gross margin starts to build. With the gross margin, you eventually cross the line and become actually a profitable ALL business. Those are the key drivers. Awesome. That's very helpful. I think you're in a very good position now as the core business doing well, it keeps growing, and you have certain layers of potential expansion that you can do with the frontline and also the pediatrics. Just give us more color on those fronts and how you can keep driving the business. Right. For the ALL side, clearly the objective is to really get the broad adoption across the physician group across the U.S. and the U.K. That's the primary focus that drives market share. We can then add, obviously, the pediatric population on top. That's a smaller number of patients, but it is meaningful from where we are. Ultimately, where I would like to see the product be positioned is in the frontline setting. What we're currently obviously seeing is we're seeing this interest for investigator-sponsored studies. That's obviously active and ongoing. What we have seen in the past in the space is that these types of studies for other products, including products like Blincyto, actually resulted in the inclusion of frontline use into the NCCN guidelines. There's different levels of evidence, et cetera, you have, et cetera. What that actually does is it creates an opportunity within the U.S. that, in fact, treatment in the frontline can be reimbursed. Obviously, in that setting and that scenario, we cannot market to that. That's clear. It's not a label. It becomes a part of a standard of care and a recommended treatment, and that's reimbursable. That's one trajectory we're on. We're looking into ways to potentially run a frontline study. That's something that we're still looking at and evaluating. The trade-off there is that also these studies tend to be very long, because you need observation time. We need to look at that versus the other investment opportunities we have in indications like in progressive MS or in other forms of autoimmune indications. We're going to make a reallocation accordingly. Yeah. That's a perfect segue to my next question, not to take away from the autoimmune side of the story. The BOBCAT data is upcoming. What should we expect from that? Also maybe just to take a step back, what's the rationale behind treating progressive MS- Yeah with CAR -T versus the other modalities? Yeah. Progressive MS or MS, in general, is very interesting because when I think back 20 years ago, anybody I would talk to about MS would have basically talked about MS as a T cell-mediated disease. That's where the focus was. It was specific T cells, and it was a huge amount of focus also on the R&D side. What we basically see today that we can probably think of MS as primarily driven by B cells. That's a huge shift in the perception in the field, and it's true across, obviously, a wide range of autoimmune diseases. What is quite unique about progressive MS or MS, in general, is that there is a correlation between the onset of MS and EBV infection. EBV actually is hosted in B cells. There is clearly part of B-cell biology that has a link there that may actually be the reason for the initial creation of autoreactive antibodies. There seems to be a link. There's a lot of pretty interesting data. Part of it is published, part of it is about to come out, and in the field and more broadly. It's very clear that the B-cells are the drivers. We have started to work on the B-cell side for quite a while using CD20 monoclonals, and there is clearly a benefit giving CD20 monoclonals. The problem, though, is that the location of the B-cells that the CD20 monoclonal can actually get to is obviously in the periphery. What the CD20 monoclonal or small molecules, for the largest part, cannot get to is actually the CNS. What we do know is that there is a substantial proportion of B cells present in the CNS itself. What we've learned through the work that was done by Georg Schett's team in Erlangen is that was the surprising part in the biology, was that the cells that were producing the autoantibodies were not mature plasma cells. They're actually plasmablasts. They were CD19 positive. That created this opportunity for this remarkable outcome, as we've seen it in our data, Georg's seen this in his data, to basically be able to see you can basically get a complete reset of the compartment. When the T cells, the CAR -T cells are gone, the compartment can actually rebuild from the marrow and actually give you a healthy B cell compartment. All of this happens, you still have your plasma cells giving you coverage for humoral response, and that's obviously important because it gives you all the protection that you need also from your vaccinations. The challenge we have in progressive MS is that it's a disease that clearly continuously deteriorates over time. It doesn't go in bursts as we have with remitting, but it literally just moves. The patients we're including are patients that have at least been on six months on CD20 monoclonal, have been on S1P inhibitors, continue to progress. They're called PIRA. That's a different way about thinking about MS as being patients that have basically, in fact, an ongoing inflammation in the absence of relapse. Now, this population has actually, when you look in their CSF, you see presence of antibody light chains. You see oligoclonal bands. There's indication of antibodies in the CSF. There is also indication of actual inflammatory activity. The idea is that with a product with obe-cel or AUCATZYL, that you have a product that can very efficiently cross the blood-brain barrier, clear out the cells that you cannot actually get to with normal therapeutic approaches. With that, actually get the drivers of that ongoing inflammation in the brain under control and removed. That's the basic hypothesis behind of what we're looking to do. It's not hypothetical in terms of the activity for our product. We have been able to show that we can actually treat patients that have CNS presence of leukemia. We have treated patients with CNS lymphoma and have very profound activity there. We had recent example that Lori Muffly from Stanford talked about at a recent recorded event that you can go and see and listen to on the website, where she talked about a patient that had so much infiltration of the brain, leukemia infiltration, that the spinal cord got compressed, and she became a paraplegic. She treated that patient. The patient was in MRD negative state at day 28. She also had full systemic disease. The CNS was cleared, and she regained control over her body. Okay. This product goes exactly where it needs to go, has exceptional activity in the brain, and it has a very good safety profile. That's why we're in MS. Awesome. That's very helpful. Looks like we're at the hour. I want to thank you, Christian. Thank you very much, Fiona. Thanks everybody for joining on, yeah, this exciting time for Autolus. Very good. Thank you very much. Thanks for your time.