Autolus Therapeutics plc

highlights for the quarter. As you can imagine, we're in the process of going through the various review processes for OVCell, both in the US as well as in Europe, and most recently now also in the UK. So that's been the primary focus from an operational perspective. I think we're making good progress and are on track with all the various interactions that we have with the regulatory authorities. The BDUFA target date, as you may remember, is November 16th this year, and we're tracking well towards that timeline. We've also initiated or have currently ongoing two phase one clinical trials. One is in pediatric ALL, which is a trial that is moving very nicely, and obviously we're excited about applying and having OV-cell evaluated in pediatric patients. That's ongoing, and we'll report, obviously, in the upcoming periods on that trial. And in addition, the phase one trial with patients that have an advanced stage, a relapsed type slash refractory stage of systemic lupus. This is the Carlisle study. We opened this study in the beginning of the year, and we dosed our first patient in the second quarter, and we continue involvement in that study as we have projected. But importantly, as we went through the course of the quarter, we did focus, I would say, very much on the update of the clinical data from our pivotal Felix study, the Phase II study that's underpinning the regulatory filings that we've made with the various authorities. Importantly, we looked at a number of aspects that we hadn't actually explored to the same extent in our prior publications and presentations around the program. One, of course, is to look for the longer-term outcome. And what we do see is that we do start to see a stabilization of both event-free survival as well as overall survival in the study, and we're starting to see a plateau forming, which is obviously something we've been very keen to evaluate, and we start seeing that now actually stabilize with more follow-up in the study. What was quite interesting, and I'll show you the data a little later as well, is that Quite typically what we have in this particular patient setting is that you actually look to consolidate the effect that you could induce with a particular therapy to induce longer-term outcome. And typically what you do is you actually have the patients undergo a stem cell transplant when they are in complete remission and ideally MRD negative, which was the case for all our patients. What was quite surprising to see, and you'll see the data in a short while as well, is that it didn't appear that the consolidation with the stem cell transplant improved the outcomes for the patients, which is very different from the other therapeutic options that are currently available in the space. We also, I think, had a closer look at the role of persistence into longer-term outcome, as well as the impact of bridging therapies, and particularly also the use of inotuzumab in patients that have very high tumor burden at time of inclusion. and where we did see a very effective approach here in terms of bridging with in a to the map. Now, in terms of the operational side of the business and the governance side, we did strengthen our board. We had Mike Bonney join as the new chair of the company and Rob Rao, who's an expert in autoimmune diseases and inflammatory diseases. So broadening of the skill set on the board and obviously a sort of the next step in terms of the evolution, both from a movement towards commercialization, which is obviously where my body's background is obviously very strong, but also an expansion from a medical perspective into adjacent indications outside of oncology, where it's clearly where Robbie Rowell's particular experience is extremely valuable. Now, in addition, obviously, we've been driving through a remarkable amount of growth and maturation of the organization as we're setting up our commercial manufacturing capabilities, getting through first regulatory filings and now keep pushing through that process and are preparing for commercialization. And there is a group of very talented leaders within the company that have really risen to the challenge and have done a fantastic job and a recognition of their work and their leadership have been promoted to senior vice presidents within the organization. This includes Brian on the regulatory side, Chris Gray, site head for Stevenage, Marcus Grill on quality, Claudia Mercedes, really operations from the manufacturing technical operations side, but also actually in a broader role than that. And then Dilip Patel, who's looking into market access and obviously did a fantastic job on that side as well. So great to see this group of leaders really grow up and within the organization and having made substantial contributions that we expect to see a lot of important contributions going forward to the business. Moving to slide number six. I would like to just briefly remind you of some of the key data that we did update on at ASCO as well as at the EHA. Both meetings happened during the course of June this year. What we did focus on is actually look at the totality of the data from the Felix study. And as you remember, the Felix study has three cohorts. By far, the largest cohort are the patients that have proper relapsed refractory disease with morphological disease, so more than 5% tumor burden. And this is the vast majority of the patients that we have treated. We have also had two small cohorts in addition that we have included in the study, a small cohort for patients that had isolated extramedullary disease. That's typically a cohort that actually gets excluded from clinical trials because of the difficult nature of the disease and the challenges of managing those patients. but also a small cohort of patients that have minimal residual disease. So disease burden below 5%, but above 10 to the minus 3. So a very relatively narrow corridor of MRD-positive disease. So that's the group. We actually analyzed the totality of that data. And as you can see, this is a total of 127 infused patients. And what we're starting to see is incredibly encouraging in terms of the patients that actually are in ongoing remission without subsequent stem cell cancer or other therapy. And that is, I think, really important because about 40% of the patients that actually continue in remission without any need for additional therapy. We also have this smaller subgroup that I'll also refer to now in the next slide, then that received a subsequent stem cell transplant. There was 18 patients. They received this transplant while being in complete remission, not only in complete remission, but also being MRD negative. So no signs of measurable disease in these patients at the time of transplant. And then obviously we had also a group of patients that were moving to other therapies or have relapsed and died. So that's the status with a median follow-up of 21 months, which was the data cut that we were using for the ASCO and DHA presentations. Moving on slide number seven, we're looking actually at the event-free survival of the patients. And as you can see, the event-free survival, and we're looking here at the two curves with and without sensing for stem cell transplant, but both curves you can see are stabilizing. and actually are starting to form a plateau, which is very indicative of a substantial portion of these patients remaining in continued remission, which is also extremely encouraging in this very difficult group of patients who have a very aggressive form of disease. When you see the curve, actually, for patients that include the stem cell transplant, that's the green curve. The blue curve are the patients where we center our patients that went on to stem cell transplant. What you see when you look at those two curves is actually a picture which is the opposite of what you would normally observe in these studies. Normally, we'd observe that patients that actually with stem cell transplant would do better and would actually give you a better, eventually, survival. What we're seeing here, it looks like the inverse, certainly not doing better, possibly doing a bit worse. if they actually receive the stem cell transplant after receiving OV-cell. Now, when we look on slide number eight at the overall survival, we see a similar picture. Certainly no evidence that a patient receiving a transplant provided them a survival benefit. And so very interesting in the sense that clearly the product on its own appears to be able to deliver a longer-term outcome and may actually be able to serve as a standalone therapy for a subset of the patients. So these are two of the key findings that we were presenting at ASCO and DHA, which we move on to slide number nine. What we're evaluating there on the left-hand side is the impact of CAR-T persistence in event-free survival in the patients. What you can see on the blue curve on the top are patients that have actually ongoing CAR-T persistence, and you can see that teeth tend to do very well, again, with the stabilization of eventually survival. Patients that lose CAR-T presence at 12 months, you can see that's the median curve, the green curve, and patients that would lose CAR-T persistence already at six months if the red curve is tracking below, indicating that indeed longer persistence of the CAR-T cells appears to be associated with a better performance on an entry survival. And just as this other surrogate to look at sort of the impact, we're looking at B-cell eplasia, and you can see also there the same type of stagger, but less differentiation between the patients. So persistence seems to be a better readout and a more reliable readout, if you want to understand the potential impact for longer-term outcome. Now, in summary, on slide number 10, quick takeaways from this pooled analysis. First of all, 40% of the responders are in ongoing remission without any subsequent therapy, and this is now with a median follow-up of 21.5 months. We clearly see evidence of a plateau forming, both in event-free survival as well as in overall survival. it does not appear that stem cell transplant-based consolidation provides an advantage for the patients and does not appear to improve event-free survival or overall survival, which is certainly an important outcome consistent with the effects we're seeing, but certainly unusual in the field so far. And clearly, we do see an interesting correlation between online persistence and improved eventually survival in these patients. With that, what I'd like to do is actually move to sort of more the operational side. And so they're getting to commercial launch readiness, move to slide number 12. As you remember, we sort of have been already very active in the preparatory steps to get ready for commercialization for quite an extended period of time already. And a lot of that, obviously, was really focused on a key area of activities. Clearly, it's creating awareness around the medical affairs activities, as you would expect, building the value stories for market access of the product. But then what's very involved is certainly the onboarding of the treatment centers. And that onboarding process is very involved, not only from a company, but also from a center perspective. That's a real effort that actually has to be put in. That goes across quite a wide range of activities that we need to sort of integrate in, whether it's related to apheresis, to the actual delivery of the product, the handling product of the product at the center, as well as additional support that we're looking to provide both to the centers and downstream to the patients as well. So it's quite an involved process, including everything related to the cell journey from the collection of the cells at the center to the manufacturing process and back. And the IT systems required to really be able to track the product and to ensure that we have a a very clear chain of identity throughout the entirety of the process. So a very substantial amount of work that's ongoing there. We're on track to have between 30 and 36 centers ready for activation by the time of an approval and are going to move once we're getting to that point would expect to be within the first year of launch at a level of about 60 centers onboarded and active with the product. So we're moving here in a very significant way as well as you know at a significant number of centers even for the initial startup phase. Now what we're particularly focusing on where we are at this point in time is really looking at the integration of the workings and testing, frankly, of all the systems required to deliver the product. So there's a lot of activity going on, making sure that all the interfaces are working between the different processes, the different systems. And that's a very involved process that we're actually engaged in in the third quarter and leading into the fourth quarter to make sure that all elements required to deliver this therapy are fully operational and tested out and actually have achieved the level of robustness required for a commercial operation. Now, on the next slide, it's just a brief view on kind of where we are and what some of those activities are that we actually need to think about at the time point when we actually do get to an approval. Obviously, we talked about the path there on the prior slide. We eventually, get to a point where hopefully around the target date, we do receive an approval for the product. Once that happens, there are several activities that need to take place. On our side and driven from the company side is really kind of the activities that are defined by the label itself. And there are certain aspects of training and activity that only can actually be finalized and run through at the time when the label is fully set and determined. And that actually has to do with a set of trainings that have to be consistent, obviously, with the approved label, as well as obviously administering a REMS strategy and training that needs to actually be implemented at that point in time. So those are elements that, from a company perspective, you'll be able to complete once an approval is in. Now, the centers themselves need to run through quite a range of activities at that point in time that really make sure that they're internally ready to be able to actually manage this type of a therapy, both from an administrative perspective as well as from an actual physical operational perspective. And you see quite a set of those activities that sort of will actually have to be worked through on the center and the inside of the center. And you can see that on the right-hand side. spell that in a bit more detail. Now, when we think about what that means from an overall timing perspective, you can see the blue curve or blue arrow up there is actually quite a range of time that we actually see where from that time point where the center actually can get activated until it actually would enroll the first patient. And we will see certainly a variability among centers in terms of the time it will take to be on board and be enrolling patients. To look at that in a bit more detail, we will go to the next slide and just look at sort of in a relatively simple way of what are some of those key activities and timelines. So completing the site accreditation, we expect will take anywhere from two to 12 weeks with the centers that we have prepared for you through the onboarding process, but are now from the time point where you can actually initiate the site activation will have take anywhere between two and 12 weeks of the patient screening, look at freezing schedule, then having that completed anywhere from one to two weeks at that point in time. And then obviously the anticipated range of delivery time of 16 days. So when you think about that and you think about it, a target date, a Purdue for target date of middle of November, and as well as sort of year-end holidays, it is reasonable to assume that the first patient dose will be happening in the early part of 2025 if we're operating on those timelines. So I think that sort of, I think, hopefully gives you a sense for what it means to start up and what are sort of reasonable assumptions around when to expect kind of first patient's dose, and then obviously it would gear up from there as we go through the course of the year. Now, with that, what I'd like to do is switch gears and just briefly talk about sort of the OB-Cell product family on slide 16, Franchise Opportunity. This is the slide you've seen before. Also, we continue to work not only on the current activity on the adult ALL side, but also working on the pediatric side as well as the autoimmune side with OB-Cell. And we'll continue to actually work on auto-122 as well as auto-8. Auto-122 mostly on the pediatric ALL side where we do additional work with the UCLH and GOSH, our partners for that program for a long period of time. And we're also obviously with Auto-8 continue to work on the multiple myeloma side, but we're also looking to sort of expand the opportunity for that program going forward as well. and we'll update you as we go forward and initiate next studies with that program when that actually happens. So with that, just a quick word on the environment on the autoimmune side of this space that many of you have watched very carefully. We had one major conference that happened in Q2, which was the ULAR conference. Interesting data set presented during the course of the conference. I think what we're starting to see is some differences that appear between programs still early days in terms of understanding what is contributing to some of the differences that are being observed, to what extent are those product driven, to what extent are those factor variability in the patients that are being treated. But certainly very interesting development that we're seeing, but also overall I think also very nice cooperation of the initial observations that we have seen with gerakshet in Erlangen that indeed there is very profound impact that can be had in those patients using CAR-T approaches. When we look at the next slide, just to remind you obviously that we have a program that has a remarkable set of similarity in terms of the clinical properties to the program that's used in Erlangen. We have, but also not only do we have a high degree of similarity in terms of the efficacy, the persistence on the pediatric ALL side where we can compare the programs directly. But also, obviously, we do have a very substantial amount of safety data, which also is an area where we can see differentiation to the program in airline, but also the differentiation to any of the other CAR-T programs that are currently commercially available. And what you see is just a summary there on the right of the table on the various key outcomes that we have seen across the various studies that we've conducted with OVCEL, and I think give you a very good view on the level of activity that we're seeing and the ability to achieve those levels of activity with a very attractive safety profile. Now, the study on slide 19, the Carlisle study, our phase one study in SLE, as I indicated, The study obviously started up, happened during the latter part of Q1 and into Q2. First patient dosed in Q2, and we're continuing to enroll in the study. We're planning six patients at a 50 million cell dose level, which obviously is a level that we know to be highly active in pediatric ALL, giving us molecular complete responses, and also a level of dose that is also highly active in the adult patient population, where, as a reminder, we're using as little as 10 million cells to induce complete remissions in patients with high tumor burden in that setting. So overall, I think we're at a very interesting stage. We're starting to sort of get first insights from a data perspective, and we'll also continue to collect that data with a plan to have an additional update on clinical data late in the year. Now, other pipeline programs on slide 21, as you remember, there's a number of other programs we're working on. I think with regards to AutoAID, I already indicated that we're looking at potentially expanding the program into additional indications. So that's something that's ongoing and will update certainly by the end of the year or the next year on sort of the trajectory we're going to be on. And then just as a quick highlight, because we haven't actually talked about that in a while, is Auto6MG. That program also is enrolling patients, and first patient actually has been treated as well in the second quarter as part of the progress that we were making during the quarter. So overall, progressing well, and we also expect additional publications to come out during the second half of the year related to our clinical programs that we've been conducting. With that, I'd like to hand over to Rob, who will then lead you through the financial results.

Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the second quarter of 2024. So I am on slide 23, where we see at the top our cash and cash equivalents. At the end of June 2024, totaled $705.9 million. That's compared to $239.6 million at the end of last year, December 31st. Our total net operating expenses for the three months ended June 30th, 2024 were $58.9 million as compared to $44.4 million for the same period of 2023. For research and development, These expenses increased from $33.2 million to $36.6 million for the three months ending June 30th, 2024, compared to the same period in 2023. This change was primarily driven by increases in operating costs related to our new manufacturing facility, employee salaries and related costs, and OB cell clinical trial and manufacturing costs. These were partially offset by a more favorable UK R&D tax credit reimbursement for the period as well. General administrative expenses increased from $11.1 million to $21.9 million for the three months ending June 30, 2024, compared to the same period last year. This increase was primarily due to salaries and other employment-related costs, driven by increased headcount supporting our overall pre-commercialization activities. And finally, for the company, net loss was $58.3 million for the three months ending June 30, compared to $45. 0.6 million for the same period in 2023. Autoless estimates that with its current cash and cash equivalents, we are well capitalized to drive the full launch and commercialization of ObieCell in relapsed refractory adult ALL, as well as to advance its pipeline development plans, including runway to date in the first pivotal study of ObieCell in autoimmune disease. I'll now hand things back to Christian to wrap up with a brief outlook on milestones. Christian.

Okay.