Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autolist Therapeutics call to discuss its first quarter 2024 financial results and business updates. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Olivia Mansour. Please go ahead.

Thanks, Tonya. Good morning or good afternoon, everyone. Thanks for joining us on today's call. With me today are Dr. Christian Eiten, our CEO, and Rob Dolsky, our CFO. So on slide two, before we begin, just like to remind you, as usual, 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 the status of clinical trials and development and or regulatory timelines for our product candidates and our expectations regarding our cash runway. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward-looking statements. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and our SEC filings, both available on the investor section of our website. Moving on to slide three, you're going to see the agenda for today's call, which is similar to usual. So Christian is going to provide an overview of our operational highlights. Rob will then take you through the financial results and Christian will conclude with upcoming milestones and will then hand over for questions. So with that, I will hand over to Christian.

Well, thank you very much, Olivia, and welcome everybody to our first quarter call. It's been a very successful quarter and obviously with a lot of activity related to OBSEL, but also obviously quite a lot of overall corporate updates as well. I'll start out with OBSEL. We started the year with the acceptance of our BLA filing, which obviously was an important event and also set the target date for the PDUFA, which is expected now for November 16th. We also managed towards the end of the quarter to get the European filing accepted. So we have now both major jurisdictions to filings under review. What was very important because it led to also the overall preparedness of the company towards commercialization was the inspection that we had of the nuclear facility by the MHRA. that was very successful and resulted in a license for both clinical and commercial supply from the facility, from the Nucleus facility. What's important to understand is that this is actually a prerequisite for us to actually be able to commercially deliver product, and that is a necessary license that we actually need to hold. Getting through that first full inspection and successfully completing that obviously was a huge accomplishment and sets us up very well for the ongoing interactions in the review process, both with the FDA as well as with the European agency. We also obviously started the phase one dose confirmation study in SLE during the quarter and also involved there our first patients. Now, when you think about data updates, the important next updates are going to be at ASCO and at EHA, which are at the end of May and the beginning or middle of June. At both meetings, we have now confirmation that we have an oral presentation of the updated Felix results, with a particular focus on longer follow-up for the study the impact of stem cell transplant that patients may have received, as well as the impact of persistence on outcome. Now, in additional, at EHA, we have two further analyses that will be presented in the form of posters. One looks at the impact of inotuzumab-based bridging regimens in the trial. And the second is on sensitive methodologies to determine the presence of CAR T cells to measure persistence and also linking that then to outcome in the study. So very significant amount of update, a lot of accomplishments through the course of this year, which sets us up very well for the further review of the program, both by the FDA and European agency. and also sets us on a very good trajectory for the target BDUFA date as well in the middle of November. Now on the operational corporate side, obviously there was a lot of activity leading into this year, which resulted in the early February timeframe in two announcements. The first was the announcement of the strategic collaboration with BioNTech, which obviously an important cornerstone in terms of our relationships that we're building. There is a significant set of options are part of this collaboration. There are options related to access that BioNTech will have for the LEED program to the nucleus manufacturing facility to support the launch of their LEED CAR-T program. That's one area that we were looking at very closely, including support on the commercial launch side. We then have, obviously, an area of activities around access to two of our pipeline programs, that's OTO-122 and OTO-6-NG. Both of those have option exercise time points that are before the start of the pivotal study in each one of these programs. We then look, in addition to those key areas, then also on the technology side, providing access to technology we've developed, particularly for the use with vivo cell therapy approaches, but also for certain applications, also in the context of other treatment modalities as well. So it's a very comprehensive relationship that we're building, and we're very excited about the relationship and the interactions that we're having with BioNTech. In parallel to the transaction with Biontech, or just following the transaction, we also did a capital markets transaction and added additional capital. Between the two transactions, we added $600 million to our balance sheet, which obviously sets us up well to deliver on the launch of OBSEL, but also gives us the ability to expand the footprint of indications, particularly for OBSEL, And that also gives us a very significant opportunity for future growth and expansion for the business. Now, we also have, as we're transitioning the company from a development stage to a commercial stage, have also actually had transitions at the level of the board that sort of actually go alongside that transformation of the company. We had, at the end of last year, Liz Leiderman and Bob Aselby joined. Obviously both a very strong capital markets experience and operating experience as well as a very strong commercial experience. And then we had in addition this quarter joined Mike Bonney who's taken over as the chair of the company from John Johnson and Ravi Rao also joined who's an expert on particularly immunology and autoimmune diseases. kind of rounds out that level and that aspect in terms of the experience base of the board so very important part of the transition that we're making sure we're sort of getting the company very well set up and forward-looking to becoming a commercial stage company and also a company that starts expanding into a broader set of indications now with that moving to the slide number six Well, I'd like to start out with OBSEL is actually answer one of the or illustrate one of the questions we're getting quite a bit, which is, well, you guys are, you know, built up this manufacturing facility, a nucleus in the UK. And but how do you actually ensure that you can actually deliver product? And is that even possible to do that within the U.S. as well as outside of the U.S.? ? And what I thought might be actually helpful is just to look at actually back at our Felix study and actually kind of just remember on what kind of environment we actually did the Felix study in. And so what you see is basically a timeline that goes from 2019 to 2023 and the actual study was conducted from the middle of 2020 towards the end of 2022 in terms of the involvement of the study. Obviously, that sort of coincides with the majority of the key period for the COVID-19 pandemic. You can see in the blue shaded area, you see all the various types of infection peaks that we've seen over time that were reported across the globe. Now, what you also see on the green line is actually the number of international flights that basically have gone in and out of the U.S. during that entire period. This is data from the U.S. government. And as you can see, this was a very challenging period from a logistics perspective because clearly you have huge variability in the number of available flights internationally. And clearly, you know, being based in the U.K. for manufacturing makes us obviously highly reliant on international flights actually taking place and the ability to really reach every site in the U.S. as well as elsewhere from our manufacturing side. Now, what was quite remarkable is when you then actually look on the small fever curve in the middle, this is actually the actual range of delivery time over that entire period for the phase two phase two conduct. And you see that for the ranges that the low end is 15 days, 30 days on the upper end. And you see literally every one of these products actually plotted on that particular jacket line. But what it means is that despite all the variability, the challenges with infection, the shutdowns of clinical centers, the shutdown of flights, and so on and so forth, all the limitations we had in terms of access, moving people and so on, had actually virtually no impact on our range of delivery time. And in fact, we were able to deliver on time for every single product. And one of the things that we obviously learned that many of you do know, given that many of you are traveling internationally quite a bit, is one of the things that we obviously have in our favor is that international flights have priority. That's where the airlines make most of their money. And those flights go on time. And that actually has been a huge asset through the pandemic and actually gave us not only a good ability to serve, but an actual advantage in terms of the robustness and stability of our logistics. This is not what you would have expected based going into the pandemic, but that's the actual reality that we have been able to see, but also obviously gives us a lot of confidence that the systems that we have put in place have to be pressure tested in an extreme way and have actually delivered throughout this challenging period. Now, if we go to the next slide, slide seven, Just as a brief reminder of the Felix study and what we're actually looking to do with the study. And I think the first thing I want to point out is that this is a study that actually included all risk categories of patients that have relapsed refractory disease, acute lymphoblastic leukemia. And what we have in there is obviously the largest group, which is the cohort A, which are patients that have disease burden that range somewhere between 5% of cells in the marrow all the way up to close to 100%. So we have this entire bucket of very high levels of disease. We also have in the middle with the core C patients that have very low levels of disease, so-called minimal residual disease. Disease levels you can pick up by flow analysis, by PCR, or by NGS sequencing. But it's important because it's basically just actually catching the relapse a little bit earlier before the standard methodology starts to pick it up. And then the last group of patients in Core C were patients that actually didn't have a relapse in the marrow, which is normally the place where you find the disease and where you typically also have the relapses. But these are patients that have isolated extramedullary disease, which is basically the disease that almost had a gain of function could actually escape the marrow, settle in another tissue, and grow out. These are particularly difficult to treat patients because also the disease has managed to actually morph to a certain extent and actually gain this ability to survive and succeed in a very different environment. So having all of these different groups is actually important when you think about this from a treating physician's perspective, because what it basically gives you, it gives you an ability to see the patients that will actually walk into your practice, the patients you care for, you'll see them represented in the study. And that doesn't often happen in clinical studies. Often clinical studies are quite selective. They're quite protected to make sure the outcome is as maximal as possible. And often with that, you actually do not have a representation of the real world. What we have with this study is a remarkable representation of the real world setting and the experience that the physicians are actually having. And this is also why this study resonates as well as it does. Now, a few things just to point out, tying to the prior part of the conversation on supply, logistics, and delivery. We actually managed to get 83% of all of the patients across the entirety of the study treated with the product. And that actually is a number that's higher than what we've seen in studies that were conducted prior to the pandemic, where you had every level of control of the patient, the selection of the patient, and every aspect on logistics. So it just tells you something about robustness and delivery alongside the study. So with that, moving to slide number eight, what we're looking at here is the event-free survival across the entirety of the experience. And as you can see, is that we see a stabilization of that curve. It looks like the curve starts to go horizontal after a certain period of time, indicative that indeed we may have a group of patients that actually have a chance for long-term outcome. Now, this is the snapshot, the data snapshot that underpins the ASH presentation. This is where this slide is from. Obviously, the next update that we're going to have at ASCO EHA will be somewhere between five and six months additional follow-up, and also gives us much more stability in the outer part of that curve, in the part of the curve where we actually are starting to see the stabilization And so we believe the update middle of this year will be important because it will give us a very good understanding whether indeed we have this robustness in the data, also in the later time points as well. Now, as you may remember, one of the things we looked at and we have pointed out in several types of conversations and presentations is that we did find that the level of disease burden the patients have prior to lymphodepletion actually was giving you a pretty good predictor of what to expect these patients will experience, on the one hand, from an efficacy perspective, but also from a safety perspective. I'll start with the efficacy side, and again, we're now looking at these event-free survival curves, but we look at it by the leukemic burden prior to lymphodepletion before we actually do the intervention. And as you can see on the blue line, these are patients that have less than 5% tumor burden, and you can see that These patients do exceptionally well. So low tumor burden not only does give us a very high overall response rate, but it also gives us obviously a very attractive long-term outcome in that patient group. Below that, in the green curve, we see the patients that are in the range of about 5% to up to 75% tumor burden. So that's a wide range of tumor burden in these patients. but it's not going to the very extreme of tumor burden in the marrow. But as you can see, these patients still do remarkably well, and you see a stabilization also in the green curve, which is very encouraging. Where you see that the patients struggle more is in that group in the orange curve, where you have patients that have more than 35% disease during that lymphocleidomastoid, which are clearly the ones that could not be controlled by bridging therapy. They have almost a by definition, refractory nature of the disease. And you do see that these patients always struggle a lot more than the other groups of patients. Now the outcome here is still substantially different to what you would have seen as an overall picture for Blinzaito. So it gives you a very good sense of terms of the actual power of the therapy, even in the worst patients that we have been treating. But it also tells you that, obviously, finding ways to actually reduce disease burden in these patients before you treat them actually has a very significant impact on outcome. Now it's not only on the side of efficacy, but also when you look on the next slide, slide 10, there's also a difference that we see in the safety signals. Now the left hand side, we see the totality of the data across all patients. And you see that what's standing out is the dark blue area. which are obviously very small. And these are the high-grade cytokine release syndrome patients or the high-grade ICANS patients. So the levels are low. They're 2% and 7%, which is substantially below any of the other T-cell engaging or CAR-T type therapies in the space. So again, a very attractive overall profile. But when we then look At the impact of disease burden, we can see that the patients that have actually less than 5% disease burden have lymphodepletion, both for CRS in the middle or for ICANs on the right-hand side. None of these patients have high-grade events, immunological toxicity events. No high-grade ICANs, no high-grade CRS. If you then look at the middle group, the middle group does still remarkably well. It has actually now, you see some of the patients that actually do experience higher-grade cytokine relief syndrome and ICANN, but it's still at a relatively low level. But what you do see is you do see somewhat of an increase, actually to a level which is, you know, similar maybe to what an overall inside the population would look like. in terms of CRS and ICANN if you're above 75% tuber burden after bridging therapy at the time of lymphodepletion. So also there, not only do you see differences in the outcome from an event-free survival perspective, but you also see differences in the risk of safety signals. Clearly, when you look at the data, it looks that patients that obviously are on the low disease burden side look to be very well manageable and very predictable, both in terms of the efficacy as well as the safety outcome, which I think will be an important factor and feature that we'll see actually worked on going forward, but I think will be an important part also in terms of the positioning of the product and where to treat the patients. In terms of commercial launch readiness, moving to slide number 12, obviously we have been talked about briefly about the trajectory here from a regulatory milestone perspective. Obviously, we're in full swing of making sure we're adequately prepared for launch. There are quite a wide range of activities. You see the left-hand side, basically the four key areas that we're sort of working with in terms of preparation. Have we managed the regions within the US? It's basically a regional view. That's kind of the way we sort of also are overlaying our organization across those. When we look in terms of the areas that we're particularly focused on, first of all, obviously in terms of communication, creating awareness, and supporting, frankly, every activity, whether it's with engagement with centers, with payers, etc., is through the medical affairs team. So very focused amount of activity that's going on, a lot of ad boards, a lot of direct engagement, and also, of course, a lot of work and support in the context of the onboarding of the centers. So that's a very significant amount of activities. A lot of that will be quite visible because it will result in presence at conferences, et cetera, and presentations and publications. There's obviously a very significant work stream around demonstrating the value of the therapy, so there's a lot of activity going on on that side. And we're looking at, obviously, a number of parameters. Important here, when you think about value, there's the obvious, you know, how much long-term benefit can you induce, you know, what is sort of the overall safety profile, et cetera. But there's also much more nuanced elements there. The fact that we have such a reduction in high-grade CRS and in high-grade ICANNs and substantially shorter events when we have high-grade events. That has a huge impact on the resource utilization at the hospitals, has a huge impact on costs, on patient management, and when you think also about the ability to sort of actually have an understanding of what to expect based on the disease burden that lives in the patient, also more predictability. there's more plannable, these treatments are more plannable and there's a way to anticipate what's going to happen to the patient and what type of support do you need to actually prepare for. That is very important because all of those are important cost drivers, that's value, but those are really important aspects that you have to not only display from a clinical perspective but then also translate that into an economic description from an operating perspective and a hospital, but also for a payer. So there's a lot of activity that's going on in that segment. I think we're well advanced on those conversations. And also a key element in terms of preparing the market that we're looking to get into. The onboarding of the centers is probably the single biggest work stream that we have, which requires us also to make sure that the product can be appropriately handled whether it is from a cell collection, handling perspective, delivery perspective, safety management, long-term outcome management. There's a lot of training involved. There is a lot of interaction and support involved. And all of that actually has a corollary in terms of systems that we are holding on our side in support of the centers and are managed through a center coordinator that really is the triaging point the centers in whatever the need is and the support required is so getting that the the centers onboarded accredited absolutely crucial this is a very involved activity also involved from the center it takes a commitment from the center takes time and we're very pleased to see the resonance that the product has and the interest and willingness of the centers to onboard product So that preparation is all ongoing and very well on track. And then we already talked about supply chain logistics. There's obviously a lot of implementation of testing as well that we do. What you also have seen is that we have mentioned before closely the transaction with Cardinal Health. That's an important transaction for us because it actually complements some of the backbone infrastructure pieces that we want to have in place and need to have in place. They also give us an element of the logistics, which allows us to actually ship products during the release process and with that also take some of the time out of the delivery time, which is important from a patient perspective and physician perspective as well. So this is kind of the preparation work that we're doing. Obviously very engaged, very involved, fantastic team on the ground, very experienced team. And we're seeing a very nice resonance and good dynamic there. Moving to the next slide and just briefly talk about the commercial manufacturing facility, the nucleus. So the image in the middle actually I took a week ago. It was one of the few sunny days we had the last few weeks in the UK. So this was the opportunity. So this is a true industrial setup for the production of cell therapy products. It's a 70,000 square foot facility and a facility that we really went from grant breaking to MHRA approval within about 27 months. So this is a remarkable delivery actually of this facility with very different approaches that we took in terms of the design, the setup of the facility, but also the taking into operation and validation of the facility. We did it in a very different mode than I think most of our colleagues in the industry would do, but it allowed us to actually massively reduce the time to get a fully functioning, fully validated, inspected facility ready, and with that obviously put us in a very strong position to be in a very good starting point with good level of capacity to support a future launch. So with that, just moving to slide 15. It's a slide you've seen before, really looking at sort of the opportunities in terms of the OviCell family of products. There's OviCell itself with opportunities both in human oncology as well as in autoimmune disease. And then there are obviously the two daughters of Avicel, Auto-122 and Auto-8, that allow us to actually give us sort of a next layer into the respective disease areas with a dual targeting approach. Now, if we move to slide 16, maybe just a few words on kind of the dynamics that we're seeing in the space, particularly when it comes to autoimmune disease. So it's a hugely active space. There's a lot of communication happening. And every time there is a paper coming out, I tend to get and we tend to get, obviously, things from some of you and how to interpret the data and how to think about it. I think in general, I think what's important to keep in mind is that almost all data points that we look at today are based on compassionate use, not clinical trials. So while the data is very impressive and quite compelling, given that we've seen long-term outcomes in patients that, frankly, it was not possible to actually get reversal of disease, and certainly no long-term outcome in these patients. So very impressive outcomes, but obviously still very low patient numbers and very limited observation. Most of what we know is from a Camarilla-like product. So this has a receptor that's identical to the Cymriacar with a modified manufacturing process, which is somewhat closer to the way we manufacture it. But that product is really what almost all the information is based on, particular ones when we look at longer-term observation. Of all the patients that were treated, be it in SLE, and scleroderma, et cetera. There's one patient so far that's been reported to actually have relapsed. That relapse happened after 18 months. Patient is still a lot better than what the patient was, but there's clearly recurrence of antibodies that was visible in that patient. And what we're starting to see is obviously that we're starting to learn where maybe the limitations are of some of these approaches. where the opportunities are, but we're still in a phase where there's a lot of learning going on. I think with that, I think it's important to keep, basically look at the data with certainly a grain of salt and remind ourselves that it is still very limited amount of data, very exciting, but limited amount of data. We've also seen now, in addition to this initial work that was done at the University of Erlangen, We've seen that first work with Linatumamab, also part in Erlang and part in Munich, to explore the use in RA patients and in single sclerosis patients, indicating that there was an ability to induce an improvement in these patients without actually showing a reset of the B-cell compartment and a lack of clarity whether these activities would actually be sustainable. What was interesting is that Georg Schett gave a recent interview, which was actually published by one of your colleagues at Cantor, and was actually asked about the data, which obviously was taken also at the University of Erlangen with the rheumatoid arthritis patients. And he indicated clearly that he would see, clearly was obviously seeing good deep responses, which seemed to be meaningful, giving meaningful clinical outcomes. But at the same time, obviously there is a lot to be learned, and it's unclear whether there would be an ability to see longer-term outcomes in this approach. So there's a lot of movement, and one of the things that certainly will be interesting to see as we're sort of thinking going forward is how many shots do we actually have in an autoimmune patient with a very active immune system to actually redose the patient And that's certainly an area where I think we start to learn, I think, as more mechanisms get in. But it's highly likely going to be one of the areas where there's going to be probably more variability introduced in outcomes. Now, on the next slide, what I'd like to do is just briefly sort of show kind of the relationship between Obicel and the product that was used at the University of Erlangen for their work. I think it's important, as I pointed out, is that the product is very similar to Kymriah, and it was designed and actually used initially for the treatment of pediatric ALL patients. So there's actually quite a good set of data available from that product, indeed. And not surprisingly, the data was very similar to the data we knew from Kymriah's original trials. So high level of activity, long persistence, two to three years persistence in these patients. And, you know, giving you in the 85%, give or take rate of molecular complete remission, as we're seeing with Kymriah. You see the reference on the right hand lower side, the Eliana study, which is what the summary of the data from the original study with Kymriah. The initial data from the pediatric experience with the airline car actually was published or presented at the ASH meeting in 2021. And there's likely going to be a publication at some point with a fuller data set. Now, what I'd like to sort of remind you of is that the key difference, obviously, between that product and our product is really in the design of the targeting domain to CD19. rather than having the high-affinity character, which is a fast on-rate with a very slow off-rate, as you can see in the blue box called FMC63, which is the binder used in that particular product. The CAT19 binder in green, that's actually the property that we see for our product, for OB-Cell, and what you can see is that we have the same on-rate, which gives you the same specificity, but about a 100-fold faster off-rate. And with that, obviously, having that differentiation that you heard us talk about quite a bit, which gives us this difference in terms of toxicity and much significant reduction in immunological toxicity, but also overall an increased level of activity that the product has. And overall, we see very similar properties of the product in ALL from an activity perspective, we see differences in toxicity, as you could also delineate from the comparison between our experience with Obicel in the light blue columns and the dark blue column, the experience with Kimraya and Yalyana study. Now, the The remarkable thing is obviously we have this similarity, we have a better safety profile, and with that we believe we're in a very attractive position to obviously move into the autoimmune space. One of the things that I'd like to highlight is that this long, persisting product in pediatric ALL had a much shorter persistence in the autoimmune patients. In fact, it went from two to three years pediatric ALL to about three months, maximally six months in autoimmune patients. This is not a difference based on amount of target available or target cells available, which some folks were thinking about. That's not what the difference is because that long persistence is also true if you have MRD positive patients or patients with extreme low levels of target cells, you still get two to three years of persistence in leukemia. Now the difference between those two settings is predominantly the ability of the immune system to map the response. And we actually assume that the key driver for the difference in persistence is in fact the ability of the patients with autoimmune disease, of their immune system, to recognize the cells eventually and clear them. And that also was corroborated by the myositis patients I mentioned before, That was actually an attempt to actually retreat with CD90 CAR, and in fact, the cells were cleared very rapidly, consistent with the fact that, indeed, the patients actually had built up over time an immunological reaction and rejection. Now, quite similarly, if you think about sub-Q delivered products and antibodies, there's also a pretty significant risk there that you might actually induce as well some immunogenicity, and that certainly has been seen with a number of products, also T-cell engagers in the past. So that's an area to watch that could actually have an impact in terms of the profiles of some of the approaches over time or the ability to redose, which certainly for some approaches seems more important than others. All right, so with that going to slide 18, the phase one study is open for involvement. We had our first center open during the course of Q1. We have now two patients enrolled, and we're well on track for the initial data that we have guided you to towards the end of the year. Just to remind you, this is a dose confirmation study. We basically translate the pediatric ALL dose in a fixed dose for adults, which is a 50 million cell dose. We don't need to do DLT periods or any of those types of restrictions within the enrollment, but we can actually enroll patients as they come without limitations of that nature. All right, so with that, Just a last view in terms of the pipeline, a bit broader view. Obviously, we're active with additional programs. Certainly, there's more activity on the AutoAid program, the Auto6NG program, and obviously both of those. We're looking forward for additional data, and we're also enrolling additional patients with Auto122 as well. All right, so with that, I'd like to actually transition. We go to financial results, and I'll hand over to Rob.